Drug dosing regimen, dosing frequency, individualisation, Steps Involved in Individualization of Dosage Regimen, optimization, variability, Clinical experience with individualization and optimization based on plasma drug levels.
This document discusses factors that contribute to variability in individual drug responses and the need to individualize drug dosing regimens. It outlines several key sources of variability, including age, body weight, gender, genetics, disease conditions, and drug interactions. For each factor, it provides examples of how that factor can influence the pharmacokinetics and pharmacodynamics of drugs and necessitate dosage adjustments tailored to the individual patient. The goal is to achieve effective therapy while avoiding toxicity by understanding and accounting for variability between patients.
This document discusses designing dosage regimens. It begins by defining dosage form as the way a drug is administered and dosage regimen as the schedule of doses over time. It then describes five methods for designing regimens: individualized, based on population averages using fixed or adaptive models, based on partial pharmacokinetic parameters, empirical, and using nomograms. Nomograms use scales to determine dosage based on patient characteristics. The document provides examples of drugs using nomograms and discusses considerations for converting intravenous to oral dosage.
The document discusses drug interactions, describing them as modifications to a drug's expected response caused by another substance. It outlines various mechanisms of interactions, including pharmacokinetic interactions that can alter absorption, distribution, metabolism and excretion, as well as pharmacodynamic interactions. Specific examples are provided to illustrate different types of interactions through various mechanisms like enzyme induction, inhibition and changes to protein binding or renal clearance.
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
The document discusses various concepts in pharmacokinetics including absorption, distribution, metabolism, and excretion of drugs in the body over time. It explains key mechanisms of absorption such as passive diffusion and carrier-mediated transport. Distribution of drugs in tissues is described using the volume of distribution concept. Metabolism and excretion of drugs via different routes is also summarized. The relationship between pharmacokinetics and pharmacodynamics is explained using drug concentration-time curves. Clinical applications of pharmacokinetic principles including therapeutic drug monitoring and dosage adjustment are also highlighted.
Elderly patients are often defined as those over 65 years old, but aging affects individuals differently. Physiologic changes that occur with aging can impact how drugs are absorbed, distributed, metabolized, and excreted from the body. Absorption and distribution may be altered due to changes in gastrointestinal function and decreases in muscle mass. Metabolism and excretion are often decreased due to reduced liver and kidney function. These changes can affect drug efficacy, safety, and risk of interactions and adverse events. When dosing elderly patients, their multiple medical conditions, polypharmacy, and risk for non-compliance must be considered. Pharmacists can help by counseling patients and monitoring their medication therapy.
This document discusses factors that contribute to variability in individual drug responses and the need to individualize drug dosing regimens. It outlines several key sources of variability, including age, body weight, gender, genetics, disease conditions, and drug interactions. For each factor, it provides examples of how that factor can influence the pharmacokinetics and pharmacodynamics of drugs and necessitate dosage adjustments tailored to the individual patient. The goal is to achieve effective therapy while avoiding toxicity by understanding and accounting for variability between patients.
This document discusses designing dosage regimens. It begins by defining dosage form as the way a drug is administered and dosage regimen as the schedule of doses over time. It then describes five methods for designing regimens: individualized, based on population averages using fixed or adaptive models, based on partial pharmacokinetic parameters, empirical, and using nomograms. Nomograms use scales to determine dosage based on patient characteristics. The document provides examples of drugs using nomograms and discusses considerations for converting intravenous to oral dosage.
The document discusses drug interactions, describing them as modifications to a drug's expected response caused by another substance. It outlines various mechanisms of interactions, including pharmacokinetic interactions that can alter absorption, distribution, metabolism and excretion, as well as pharmacodynamic interactions. Specific examples are provided to illustrate different types of interactions through various mechanisms like enzyme induction, inhibition and changes to protein binding or renal clearance.
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
The document discusses various concepts in pharmacokinetics including absorption, distribution, metabolism, and excretion of drugs in the body over time. It explains key mechanisms of absorption such as passive diffusion and carrier-mediated transport. Distribution of drugs in tissues is described using the volume of distribution concept. Metabolism and excretion of drugs via different routes is also summarized. The relationship between pharmacokinetics and pharmacodynamics is explained using drug concentration-time curves. Clinical applications of pharmacokinetic principles including therapeutic drug monitoring and dosage adjustment are also highlighted.
Elderly patients are often defined as those over 65 years old, but aging affects individuals differently. Physiologic changes that occur with aging can impact how drugs are absorbed, distributed, metabolized, and excreted from the body. Absorption and distribution may be altered due to changes in gastrointestinal function and decreases in muscle mass. Metabolism and excretion are often decreased due to reduced liver and kidney function. These changes can affect drug efficacy, safety, and risk of interactions and adverse events. When dosing elderly patients, their multiple medical conditions, polypharmacy, and risk for non-compliance must be considered. Pharmacists can help by counseling patients and monitoring their medication therapy.
Here are the key steps to solve this problem:
1) Convert infant weight to kg: 11 lbs = 5 kg
2) Use Clark's rule to calculate infant dose:
Weight (in lb) X Adult Dose = Infant Dose
150 lb
11 lb X 4 mg/kg = 2.4 mg/kg
150 lb
So the dose of penicillin G for the 11 lb infant is 2.4 mg/kg every 4 hours.
Dosage adjustment in Hepatic Failure.pdfsamthamby79
This document discusses dosage adjustment considerations in patients with hepatic impairment. It covers hepatic drug clearance and how it is affected by factors like hepatic blood flow and extraction ratio. Drugs are classified as having high, intermediate, or low extraction ratios. The Child-Pugh score and MELD classification scheme are presented as tools to assess liver disease severity and determine appropriate dosage adjustments. Recommendations are provided for various drug types based on their extraction ratios and protein binding properties.
The document discusses dosing considerations for obese patients, noting that obesity can impact the pharmacokinetics of drugs through changes in volume of distribution, metabolism, and excretion due to alterations in body composition and organ function. It provides guidelines for calculating loading and maintenance doses based on whether drugs are primarily distributed in lean or fat mass, and recommends estimating glomerular filtration rate and renal clearance using adjusted body weight formulas for obese patients.
This document discusses inhibition and induction of drug metabolism. It describes how some drugs can decrease (inhibit) or increase (induce) the activity of enzymes involved in drug metabolism. Examples are given of drugs that inhibit the metabolism of other drugs, leading to increased levels and potential toxicity. Inhibition can occur directly by interacting with the enzyme or indirectly by other mechanisms. The document also discusses inhibition of biliary secretion, an important route of drug excretion, and how this can cause drug-drug interactions by affecting drug levels.
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
This document discusses genetic polymorphisms in drug transporters and drug targets. It defines genetic polymorphisms as variations in gene sequences that occur in at least 1% of the general population. The most common type is a single nucleotide polymorphism (SNP) resulting from a change in a single nucleotide base pair. SNPs can be synonymous or non-synonymous, with non-synonymous SNPs potentially altering the protein's structure and function. The document outlines various drug transporters including P-glycoprotein and discusses genetic polymorphisms that can affect their expression and activity levels. It also discusses how genetic polymorphisms in drug metabolizing enzymes and drug receptors can influence drug response and side effects.
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
various measures for the measurement of outcome such as incidence prevalence and other drug us measures are briefly discussed here with suitable examples and equations
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
The document discusses various methods for designing dosage regimens, including individualized regimens based on pharmacokinetic measurements, population-based regimens, empirical regimens, and regimens based on partial pharmacokinetic data or nomograms. It also covers considerations for converting patients from intravenous to oral drug administration through sequential, switch, or step-down methods based on pharmacokinetic principles and calculations using steady-state drug concentrations and clearance. An example calculation is provided to determine an appropriate oral theophylline dosage based on intravenous aminophylline infusion rates.
Hepatic disease can significantly alter the pharmacokinetics and pharmacodynamics of drugs due to changes in drug metabolism, transport, and clearance in the liver. The degree of liver impairment is assessed using tests like the Child-Pugh score, with higher scores indicating more severe impairment. Drugs eliminated primarily by the liver or highly bound to albumin are more likely to require dosage adjustments in patients with hepatic disease due to potential changes in metabolism, protein binding, and clearance. The fraction of the drug metabolized and properties of its active metabolites also influence whether dosage adjustment is necessary.
The kidney plays an important role in regulating fluids, electrolytes, and removing waste from the body. Impairment of kidney function affects drug pharmacokinetics. Common causes of kidney failure include disease, injury, drug toxicity, infections, diabetes, toxins, and reduced blood flow. Acute kidney problems or trauma can lead to uremia where filtration is impaired, causing excess fluid and waste to accumulate. Uremic patients may have changes in drug absorption, distribution, and clearance. Dosage adjustments are often needed based on a patient's kidney function and drug properties to safely treat uremic patients.
Definition and scope of Pharmacoepidemiology ABUBAKRANSARI2
In these slides I shared the information of definition and scope of pharmacoepidemiology. Types of studies - cohort studies, cross-sectional studies etc.
Therapeutic drug monitoring of organ transplantation drugsDr. Ramesh Bhandari
1) The document discusses the therapeutic drug monitoring of cyclosporine, an immunosuppressant commonly used following organ transplantation.
2) Cyclosporine has variable absorption and significant inter-patient variability requiring therapeutic drug monitoring to maintain trough concentrations between 100-400 mcg/L.
3) Factors like CYP3A inhibitors/inducers and foods can impact cyclosporine levels, requiring dosage adjustments to be made based on concentration monitoring.
This document discusses population pharmacokinetics and analyzing population pharmacokinetic data. It notes that while all humans are alike as a species, there are differences between populations in drug metabolism and responses. These differences are due to genetic variations between racial/ethnic groups. It describes several methods for analyzing population pharmacokinetic data, including NONMEM, which fits concentration data from all subjects simultaneously to estimate population parameters and variances, and standard two-stage methods.
This document discusses dose adjustment in patients with renal impairment. It covers several key topics:
1. The kidney's role in regulating fluids, electrolytes, waste removal, and drug excretion. Impaired kidney function affects drug pharmacokinetics.
2. Approaches for dose adjustment based on estimating remaining renal function and drug clearance. Dose, dosing interval, or both may be adjusted to maintain therapeutic drug levels.
3. Methods for estimating glomerular filtration rate and measuring kidney function using markers like inulin, creatinine, and urea. Creatinine clearance is commonly used in clinical practice.
4. Considerations for dose adjustment in patients on dialysis, as
This document discusses the individualization of drug dosage regimens to account for variability between patients. It notes that while humans are alike as a species, there are differences between individuals that impact their responsiveness to drugs. Failing to tailor drug administration to each patient can lead to ineffective therapy in some or toxicity in others. The document outlines the main sources of variability in pharmacokinetics as biological factors like age, weight, gender and genetics, environmental factors like drug interactions and disease states, and cultural factors. It discusses approaches to designing individualized dosage regimens based on estimating pharmacokinetic parameters in individual patients or using population averages with adjustments. The key parameters that can be adjusted are dose size and dosing frequency.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals of clinical pharmacokinetics include enhancing efficacy and decreasing toxicity of a patient's drug therapy.
The success of drug therapy is highly dependent on the choice of the drug, the drug product, and the design of the dosage regimen. The choice of the drug is generally made by the physician after careful patient diagnosis and physical assessment.
Here are the key steps to solve this problem:
1) Convert infant weight to kg: 11 lbs = 5 kg
2) Use Clark's rule to calculate infant dose:
Weight (in lb) X Adult Dose = Infant Dose
150 lb
11 lb X 4 mg/kg = 2.4 mg/kg
150 lb
So the dose of penicillin G for the 11 lb infant is 2.4 mg/kg every 4 hours.
Dosage adjustment in Hepatic Failure.pdfsamthamby79
This document discusses dosage adjustment considerations in patients with hepatic impairment. It covers hepatic drug clearance and how it is affected by factors like hepatic blood flow and extraction ratio. Drugs are classified as having high, intermediate, or low extraction ratios. The Child-Pugh score and MELD classification scheme are presented as tools to assess liver disease severity and determine appropriate dosage adjustments. Recommendations are provided for various drug types based on their extraction ratios and protein binding properties.
The document discusses dosing considerations for obese patients, noting that obesity can impact the pharmacokinetics of drugs through changes in volume of distribution, metabolism, and excretion due to alterations in body composition and organ function. It provides guidelines for calculating loading and maintenance doses based on whether drugs are primarily distributed in lean or fat mass, and recommends estimating glomerular filtration rate and renal clearance using adjusted body weight formulas for obese patients.
This document discusses inhibition and induction of drug metabolism. It describes how some drugs can decrease (inhibit) or increase (induce) the activity of enzymes involved in drug metabolism. Examples are given of drugs that inhibit the metabolism of other drugs, leading to increased levels and potential toxicity. Inhibition can occur directly by interacting with the enzyme or indirectly by other mechanisms. The document also discusses inhibition of biliary secretion, an important route of drug excretion, and how this can cause drug-drug interactions by affecting drug levels.
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
This document discusses genetic polymorphisms in drug transporters and drug targets. It defines genetic polymorphisms as variations in gene sequences that occur in at least 1% of the general population. The most common type is a single nucleotide polymorphism (SNP) resulting from a change in a single nucleotide base pair. SNPs can be synonymous or non-synonymous, with non-synonymous SNPs potentially altering the protein's structure and function. The document outlines various drug transporters including P-glycoprotein and discusses genetic polymorphisms that can affect their expression and activity levels. It also discusses how genetic polymorphisms in drug metabolizing enzymes and drug receptors can influence drug response and side effects.
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
various measures for the measurement of outcome such as incidence prevalence and other drug us measures are briefly discussed here with suitable examples and equations
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
The document discusses various methods for designing dosage regimens, including individualized regimens based on pharmacokinetic measurements, population-based regimens, empirical regimens, and regimens based on partial pharmacokinetic data or nomograms. It also covers considerations for converting patients from intravenous to oral drug administration through sequential, switch, or step-down methods based on pharmacokinetic principles and calculations using steady-state drug concentrations and clearance. An example calculation is provided to determine an appropriate oral theophylline dosage based on intravenous aminophylline infusion rates.
Hepatic disease can significantly alter the pharmacokinetics and pharmacodynamics of drugs due to changes in drug metabolism, transport, and clearance in the liver. The degree of liver impairment is assessed using tests like the Child-Pugh score, with higher scores indicating more severe impairment. Drugs eliminated primarily by the liver or highly bound to albumin are more likely to require dosage adjustments in patients with hepatic disease due to potential changes in metabolism, protein binding, and clearance. The fraction of the drug metabolized and properties of its active metabolites also influence whether dosage adjustment is necessary.
The kidney plays an important role in regulating fluids, electrolytes, and removing waste from the body. Impairment of kidney function affects drug pharmacokinetics. Common causes of kidney failure include disease, injury, drug toxicity, infections, diabetes, toxins, and reduced blood flow. Acute kidney problems or trauma can lead to uremia where filtration is impaired, causing excess fluid and waste to accumulate. Uremic patients may have changes in drug absorption, distribution, and clearance. Dosage adjustments are often needed based on a patient's kidney function and drug properties to safely treat uremic patients.
Definition and scope of Pharmacoepidemiology ABUBAKRANSARI2
In these slides I shared the information of definition and scope of pharmacoepidemiology. Types of studies - cohort studies, cross-sectional studies etc.
Therapeutic drug monitoring of organ transplantation drugsDr. Ramesh Bhandari
1) The document discusses the therapeutic drug monitoring of cyclosporine, an immunosuppressant commonly used following organ transplantation.
2) Cyclosporine has variable absorption and significant inter-patient variability requiring therapeutic drug monitoring to maintain trough concentrations between 100-400 mcg/L.
3) Factors like CYP3A inhibitors/inducers and foods can impact cyclosporine levels, requiring dosage adjustments to be made based on concentration monitoring.
This document discusses population pharmacokinetics and analyzing population pharmacokinetic data. It notes that while all humans are alike as a species, there are differences between populations in drug metabolism and responses. These differences are due to genetic variations between racial/ethnic groups. It describes several methods for analyzing population pharmacokinetic data, including NONMEM, which fits concentration data from all subjects simultaneously to estimate population parameters and variances, and standard two-stage methods.
This document discusses dose adjustment in patients with renal impairment. It covers several key topics:
1. The kidney's role in regulating fluids, electrolytes, waste removal, and drug excretion. Impaired kidney function affects drug pharmacokinetics.
2. Approaches for dose adjustment based on estimating remaining renal function and drug clearance. Dose, dosing interval, or both may be adjusted to maintain therapeutic drug levels.
3. Methods for estimating glomerular filtration rate and measuring kidney function using markers like inulin, creatinine, and urea. Creatinine clearance is commonly used in clinical practice.
4. Considerations for dose adjustment in patients on dialysis, as
This document discusses the individualization of drug dosage regimens to account for variability between patients. It notes that while humans are alike as a species, there are differences between individuals that impact their responsiveness to drugs. Failing to tailor drug administration to each patient can lead to ineffective therapy in some or toxicity in others. The document outlines the main sources of variability in pharmacokinetics as biological factors like age, weight, gender and genetics, environmental factors like drug interactions and disease states, and cultural factors. It discusses approaches to designing individualized dosage regimens based on estimating pharmacokinetic parameters in individual patients or using population averages with adjustments. The key parameters that can be adjusted are dose size and dosing frequency.
Clinical pharmacokinetics is the application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient. Primary goals of clinical pharmacokinetics include enhancing efficacy and decreasing toxicity of a patient's drug therapy.
The success of drug therapy is highly dependent on the choice of the drug, the drug product, and the design of the dosage regimen. The choice of the drug is generally made by the physician after careful patient diagnosis and physical assessment.
This document summarizes a seminar on applying pharmacokinetics in new drug development and dosage form design. [1] It discusses how pharmacokinetic parameters can be used to design dosage regimens, predict and explain drug interactions, and individualize treatment for different populations. [2] Dose size and dosing frequency, pharmacokinetics of drug interactions, and dosing adjustments for renal or hepatic disease, obesity, children, and the elderly are some of the specific topics covered. [3] The seminar aims to describe how pharmacokinetics can optimize drug therapy through properties dosage selection and monitoring.
This document summarizes a seminar on applying pharmacokinetics in new drug development and dosage form design. [1] It discusses how pharmacokinetic parameters can be used to design dosage regimens, predict and explain drug interactions, and individualize treatment for different populations. [2] Dosage adjustment considerations for special populations like neonates, children, elderly, hepatically or renally impaired patients are also reviewed. [3] The document emphasizes that therapeutic drug monitoring is important for optimizing drug therapy for individual patients.
This document summarizes a seminar on applying pharmacokinetics in new drug development and dosage form design. It discusses how pharmacokinetic parameters can be used to design dosage regimens, predict and explain drug interactions, and individualize treatment for special populations. Factors like dose size, dosing frequency, hepatic and renal function, age, weight, and disease states are considered when designing optimized dosage regimens. Therapeutic drug monitoring is also discussed as a way to evaluate patient response and adjust treatment as needed.
Pediatric Drug calculations |drug calculation formulasNEHA MALIK
Most drugs in children are dosed according to body weight (mg/kg) or body surface area (BSA) (mg/m2). Care must be taken to properly convert body weight from pounds to kilograms (1 kg= 2.2 lb) before calculating doses based on body weight. Doses are often expressed as mg/kg/day or mg/kg/dose, therefore orders written "mg/kg/d," which is confusing, require further clarification from the prescriber.
This document discusses approaches to designing dosage regimens and individualizing dosage regimens for patients. It covers topics like dose size and frequency, drug accumulation during multiple dosing, loading and maintenance doses, sources of variability between patients, and dosing considerations for specific patient populations like neonates/children, elderly patients, and patients with renal or hepatic impairment. The key approaches discussed are empirical dosage regimens, individualized regimens based on pharmacokinetics, and regimens based on population averages using fixed or adaptive models.
The document discusses factors that can modify drug effects, including individual differences in pharmacokinetics, receptors, and physiological states. It describes several factors such as body size, age, sex, genetics, disease states, and other drugs that can impact drug response either quantitatively by altering concentrations or qualitatively by changing the type of response. Understanding these modifying factors is important for physicians to consider when determining individualized drug dosing and avoiding adverse reactions.
This document discusses key aspects of posology (dose determination) including:
1. Posology refers to determining appropriate drug doses. The goal is to provide optimal therapeutic effects at the lowest possible dose.
2. Many factors affect drug dosage including age, weight, pathological state, tolerance, and drug interactions. Dosage may need adjustment based on these factors to avoid toxicity or lack of effect.
3. Routes of administration and pharmaceutical formulations can also impact drug absorption and dosage requirements. Oral doses are usually higher than parenteral doses due to incomplete oral absorption. Smaller drug particles may require lower doses due to faster absorption.
The science of dosage or posology (from Greek posos, how much, and logos, study) is a branch of pharmacology and therapeutics concerned with ‘treatment dosage’ and ‘dosage regimen’. Establishing optimum dosage underpins every clinical development plan for novel therapeutic candidates. Failure to select the adequate drug dose is a leading culprit for regulatory delays or denial of initial applications for new drugs and, more generally, inadequate dose selection contributes to the high attrition rate of pivotal clinical trials.
Posology refers to the dosing of medications. Several factors affect drug dosing, including age, weight, sex, and medical conditions. Dosing is aimed at producing the optimal therapeutic effect with the lowest possible dose. The standard adult dose serves as the starting point, but may need adjustment based on individual patient characteristics. Careful consideration of dosing is especially important for vulnerable groups like children, elderly, and pregnant/nursing women. The route of administration, formulation, and timing of doses can also impact absorption and effectiveness. Close monitoring is sometimes needed when adjusting or prolonging drug therapy.
The document discusses various factors used to determine drug dosages for pediatric and geriatric patients, including age, weight, body surface area, and medical condition. It provides examples of calculating dosages based on these factors and describes special considerations for cancer chemotherapy dosing, such as using standard regimens, abbreviations for drugs, and dosing based on body weight or surface area.
The document discusses various factors that contribute to inter-individual variability in drug response, including age, body weight, gender, genetics, disease conditions, and drug interactions. Key sources of variability include differences in absorption, distribution, metabolism, and excretion of drugs across patients. Pharmacists can help individualize drug dosing regimens for patients based on an understanding of these sources of variability.
This document discusses factors that influence drug dosage and action in the body. It describes how dosage forms deliver drugs to target sites and factors like accurate dosing, protection, and sustained release. Physiological factors like age, sex, disease states, and genetics can impact drug metabolism and response. Environmental influences like smoking can also modify drug action. Individuals show wide variability in how drugs are handled and their effects, requiring personalized dosing to achieve optimal therapeutic outcomes.
The document discusses various aspects of therapeutic regimens including dose-response curves, drug toxicity, dosage regimens, and factors to consider in designing drug dosages. Specifically, it covers how dose-response curves determine the required dose and frequency for a drug, symptoms and treatments for drug toxicity, methods for designing dosage regimens based on population averages or individual pharmacokinetics, and special considerations for dosing drugs in infants, children, and the elderly. Clinical trials are also mentioned as a way to study the safety and efficacy of medical strategies.
This document discusses various methods for calculating drug doses, including definitions of dose-related terms and factors considered in dose determination such as age, weight, body surface area, organ function, and condition being treated. Equations are provided for calculating the size of a dose, number of doses, or total quantity based on one given value. Examples demonstrate dose calculations for specific patients based on weight, body surface area, and dosing tables. Nomograms are also described as a tool for determining body surface area.
- Clinical pharmacokinetics applies pharmacokinetic principles to optimize drug therapy for individual patients. It helps enhance efficacy and reduce toxicity.
- The 4 basic principles are absorption, distribution, metabolism, and elimination which determine how the body processes a drug over time. Factors like solubility, vascularity and metabolism impact these principles.
- Key pharmacokinetic parameters include volume of distribution, clearance, half-life, and bioavailability which describe the time course and extent of drug exposure in the body. Pharmacokinetic models can be used to analyze drug behavior.
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
PK and Drug Therapy in pediatrics, geriatrics and pregnancy & LactationSreeja Saladi
This document summarizes key points about pharmacokinetics and drug therapy in geriatrics, pediatrics, pregnancy, and lactation. It discusses how age-related physiological changes can impact absorption, distribution, metabolism, and excretion of drugs in geriatric and pediatric patients. It also describes factors that influence placental transfer and breastmilk exposure of drugs in pregnancy and lactation. Providing safe and effective drug therapy to these special populations requires consideration of altered pharmacokinetics and potential risks to the fetus or breastfeeding infant.
Similar to Individualisation and optimization of drug dosing regimen (20)
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...Donc Test
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
2. CONTENT
1. Introduction
2. Individualization of drug dosing regimen
Introduction
Advantages
Sources of variability
1. Steps Involved in Individualization of Dosage Regimen
2. Optimizing Dosage Regimen
3. Clinical experience with individualization and optimization based
on plasma drug levels
2
3. INTRODUCTION
Dosage Regimen - Dosage regimen is defined as the manner in which
the drug is taken.
For some drugs like analgesics single dose is efficient for optimal
therapeutic effect however the duration of most illnesses are longer than
the therapeutic effect produced by a single dose, In such cases drugs are
required to be taken on a repetitive bases over a period of time
depending upon the nature of illness.
An optimal multiple dosage regimen is the one in which the drug is
administered in suitable doses with sufficient frequency that ensures
maintenance of plasma conc. within the therapeutic window for entire
duration of therapy.
3
5. INDIVIDUALIZATION OF DRUG DOSING
REGIMEN
It is the most accurate approach and is based on the pharmacokinetics
of drug in the individual patient.
The approach is suitable for hospitalized patients but is quite expensive.
Same dose of drug may produce large differences in pharmacologic
response in different individuals, this is called as Intersubject
variability.
In other words it means that the dose required to produce a certain
response varies from individual to individual.
5
6. The main objective of individualization is aimed at optimizing the dosage
regimen.
An inadequate therapeutic response calls for a higher dosage whereas drug
related toxicity calls for a reduction in dosage.
Thus in order to aid individualization, a drug must be made available in dosage
forms of different dose strengths. The number of dose strengths in which a
drug should be made available depends upon two major factors:
1. The therapeutic index of the drug, and
2. The degree of inter subject variability.
Smaller the therapeutic index and greater the variability, more the
number of dose strengths required.
6
7. Advantages of Individualization :
Individualization of dosage regimen help in development of dosage
regimen which is specific for the patient.
Leads to decrease in Toxicity and side effects and increase in
pharmacological drug efficacy.
Leads to decrease in allergic reactions of the patient for the drug if any.
Patient compliance increases.
7
8. SOURCES OF VARIABILITY
1. Pharmacokinetic Variability –
Due to difference in drug concentration at the site of action (as reflected from plasma
drug concentration) because of individual differences in Drug absorption, Distribution,
Metabolism and Excretion.
Major causes are genetics, disease, age, body wt. & drug-drug interactions
2. Pharmacodynamics Variability –
Which is attributed to differences in effect produced by a given drug concentration.
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9. Steps Involved in Individualization of Dosage Regimen
Based on the assumption that all patients require the same plasma conc. range for
therapeutic effectiveness, the steps involved in the individualization of dosage
regimen are :
Estimation of Pharmacokinetic Parameters in individual patients and to evaluate
the degree of Variability.
Attributing the Variability to some measurable characteristics such as hepatic or
renal diseases, Age, weight etc.
Designing the new dosage regimen from the collected data.
The design of new dosage regimen involves –
1. Adjustment of dosage or
2. Adjustment of dosing interval or
3. Adjustment of both dosage and dosing interval.
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10. A: Dosing of Drugs In Obese Patients:
The apparent volume of distribution is greatly affected by changes in body
weight since the latter is directly related to vol. of various body fluids.
The Ideal Body Weight (IBW) for men and women can be calculated from
following formulae:
IBW (Men) = 50 kg +/- 1kg/2.5cm above or below 150cm in height.
IBW (Women) = 45kg +/- 1kg/2.5cm above or below 150cm in height.
Any person whose body Weight is more than 25% above the IBW is considered
Obese.
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11. B: Dosing of Drugs in Neonates, Infants and Children
Neonates, Infants and children require different dosages than that of adults
because of differences in the body surface area, TBW and ECF on per kg
body weight basis.
Dose for such patients are calculated on the basis of their body surface area
not on body weight basis.
The surface area in such patients are calculated by Mosteller’s equation :
SA (in m2) = (Height x Weight)1/2
60
Infants and children require larger mg/kg doses than adults because:
Their body surface area per kg body weight is larger and hence
Larger volume of distribution (particularly TBW and ECF)
TBW- Total body water. ECF- Extra cellular fluid.
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12. The child's Maintenance dose can be calculated from adult dose by the
following by the following equation :
Child’s dose = SA of child in m2 x Adult dose
1.73
Where 1.73 is surface area in m2 of an avg. 70kg adult.
Since the surface area of a child is in proportion to the body weight
according to the following equation:
SA(in m2)= Body weight (in kg)
The following relationship can also be written for child’s dose:
Child dose = Wt. of child in kg x Adult dose
70
12
13. As the TBW in neonates is 30% more than that in adults,
The Vd for most water soluble drugs is larger in infants and
The Vd for most lipid soluble drugs is smaller .
Accordingly the dose should be adjusted.
C: Dosing of drugs in Elderly
Drug dose should be reduced in elderly patients because of general
decline in body function with age.
The lean body mass decreases and body fat increases by almost 100% in
elderly persons as compared to adults.
Vd of water soluble drugs may decrease and that of lipid soluble drugs
like diazepam increases with age.
Age related changes in renal and hepatic functions greatly alters the
clearance of drugs.
13
14. The equation that allows calculation of maintenance dose in such patients is
given as follows :
Patients dose = (weight in Kg) (140 - age in years) x adult dose
1660
D: DOSING OF DRUGS IN HEPATIC DISEASE
Disease is a major source of variations in drug response. Both
pharmacokinetics and pharmacodynamics of many drugs are
altered by diseases other than the one which is being treated. The
influence of hepatic disorder on drug availability and disposition is
unpredictable because of the multiple effects that liver disease
produces – effects on drug metabolizing enzymes, on drug
binding and on hepatic blood flow. Hence, a correlation between
altered drug pharmacokinetics and hepatic function is often
difficult. 14
15. For example, unlike excretion, there are numerous pathways by which a
drug may be metabolized and each is affected to a different extent in
hepatic disease.
Therefore the drug dosage should be reduced in patients with hepatic
dysfunction since clearance is reduced and availability is increased in such
a situation.
E: DOSE ADJUSTMENT IN RENAL FAILURE
Drug in patients with renal impairment have altered pharmacokinetic
profile.
Their renal clearance and elimination rate are reduced, the elimination half-
life is increased and apparent volume of distribution altered.
Since dose must be altered depending upon renal function in such patient.
To calculate dose in case of renal failure , the regimen may be adjusted by
reduction in dosage or increase in dosing interval or a combination of both
15
16. OPTIMIZING DOSAGE REGIMENS
Incorporating the patient's characteristics in the process of initiating a
drug dosage regimen is an important step toward optimization of drug
therapy, but it does not guarantee the success of the therapy.
We still need to evaluate the outcome of the treatment and we still find
in some cases that the therapeutic objective has not been achieved.
Traditionally, the management of drug therapy has been accomplished
by monitoring the incidence and intensity of both desired therapeutic
effects and undesired adverse effects.
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17. CLINICAL EXPERIENCE WITH INDIVIDUALIZATION
AND OPTIMIZATION
BASED ON PLASMA DRUG LEVELS
A: ANTIARRHYTHMIC DRUGS
1- Quinidine : It is useful for treatment of atrial and ventricular
arrhythmia. It is usually administered orally but may be given by
intramuscular or intravenous injection. It has a half-life of about 6 to 7 hrs.
When usual dosages of quinidine are given to patients on enzyme-
inducing drugs, such as phenobarbital, phenytoin, or rifampin, low sub-
therapeutic blood levels of quinidine are likely to result. Higher than
usual dosages of quinidine are required in these patients.
17
18. Quinidine concentrations of about 3 to 8µg/ml are considered
therapeutic when nonspecific assay methods are used. With a high
performance liquid chromatography assay procedure antiarrhythmic
effects are associated with serum quinidine levels of 2 to 5 µg/ml.
The frequency of gastrointestinal disturbances increases with quinidine
levels above 5 µg/ml; cardiovascular disturbances are a concern at
concentrations exceeding 8 µg/ml.
2- Lidocaine
Lidocaine is the most frequently used intravenous antiarrhythmic agent
for the short term management of ventricular arrhythmias.
The half-life of lidocaine is about 2 hr.
In some patients, the clearance of lidocaine decreases with continuous
infusion: dosage reduction may be required during therapy.
18
19. Coadministration of cimetidine or propranolol. which decreases liver
blood flow and inhibits hepatic metabolism, may also require dosage
reduction of lidocaine.
Plasma levels of lidocaine less than 1.5 µg/ml are usually ineffective.
The usual therapeutic lidocaine concentration range is 1.5 to 4.0 µg/ml,
but levels up to 8 µg/ml may be needed in some patients. These higher
concentrations may be associate with central nervous system (CNS)
toxicity and cardiovascular depression. Lidocaine levels exceeding 8
µg/ml may be associated with seizures and serious cardiovascular
disturbances.
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20. B. ANTIBIOTICS
1- Aminoglycoside Antibiotics
The aminoglycoside antibiotics are effective in treating
pneumonia, urinary tract, soft tissue, burn wound, and other
systemic infections caused by gram-negative organisms.
All aminoglycosides are ototoxic and nephrotoxic and have a
relatively low therapeutic index.
The major elimination route for the aminoglycosides is renal
excretion, largely by way of glomerular filtration.
The half-lives of gentamicin and tobramycin in patients with
normal renal function are variable but avg about 2.5hr.
Patients with impaired renal function eliminate the
aminoglycosides more slowly and require reduced dosage.
Infants less than 7 days of age and elderly patients also require
lower dosages.
20
21. 2- Vancomycin
Vancomycin is a glycopeptide antibiotic commonly used in the
treatment of serious Gram-positive infections. Nephrotoxicity is often
cited as an adverse effect, especially when high dose therapy is used for
a prolonged duration.
Nephrotoxicity was found to be significantly higher if the steady-state
vancomycin concentrations were >25–32 μg/mL.
C: ANTICONVULSANTS
For most epileptic patients, long-term drug therapy is the only practical
form of treatment. Therapy usually continues for at least 3 years and
often for a lifetime. In many clinics and institutions, monitoring of
plasma anticonvulsant levels is a part of the routine management of
patients with epilepsy.
21
22. 1- Phenytoin
No drug has a greater need for therapeutic drug concentration monitoring
and individualized dosing than phenytoin. A relationship between drug
concentration in plasma and daily dose is almost nonexistent because
phenytoin is poorly absorbed, highly plasma protein bound, and subject to
nonlinear, capacity-limited metabolism. Despite these problems, it is the
most frequently prescribed anticonvulsant drug for the management of
grandmal and partial seizures.
Optimum phenytoin efficacy is achieved in most patients with serum
concentrations in the range of 10 to 20µg/ml.
Concentration-related CNS toxicity of phenytoin is generally observed at
serum concentrations above 20 µg/ml. As serum levels rise, so do the
frequency and severity of side effects.
22
23. Children metabolize phenytoin more rapidly than do adults and may
require 2 or 3 times larger mg/kg daily doses (up to 15 mg/kg per day)
than do adults.
The dosage of phenytoin may need to be increased during pregnancy
because of the increased clearance of the drug during this period.
2- Phenobarbital
In general, phenobarbital is effective in all convulsive disorders ; it has
been used as an anticonvulsant drug since 1912.
The half-life of phenobarbital ranges from 50 to 120 hr in adults and from
40 to 70 hr in children. Because of its long half-life, phenobarbital is
usually given to adults once a day at bedtime. Children sometimes require
twice-a-day dosing. Approximately 2 to 3 weeks may be required to reach
steady-state levels of phenobarbital in plasma.
23
24. Plasma concentrations of 15 to 40 µg/ml are usually required for
adequate therapeutic effect. Plasma phenobarbital levels exceeding 60
µg/ml result in lethargy, coma, but habitual barbiturate abusers may
tolerate much higher concentration.
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