This document provides an introduction to pharmacokinetics, biopharmaceutics, pharmacodynamics, clinical pharmacokinetics, and toxicokinetics. It discusses how pharmacokinetics describes the absorption, distribution, metabolism and excretion of drugs in the body. Biopharmaceutics examines how the physical properties of drugs and dosage forms influence drug absorption. Pharmacodynamics studies the biochemical and physiological effects of drugs. Clinical pharmacokinetics applies these principles to optimize drug therapy for patients. Toxicokinetics and clinical toxicology evaluate adverse drug effects.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
INTRODUCTION TO BIOPHARMACEUTICS , pharmacokinetics, pharmacodynamics and the...krishna keerthi
Biopharmaceutics is a field within the pharmaceutical science that explores the relationship between the formulation of a drug and its pharmacological effects. it delves into how a drug is absorbed, distributed, metabolized, and excreted in the body, aiming to optimize drug delivery for enhanced therapeutic outcomes. this discipline integrates principles of pharmacokinetics , pharmacodynamics and pharmaceutical technology to understand the factors influencing drug bioavailability and efficacy.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
This presentation will give the students a basic knowledge about the pharmacokinetics of durgs. It will help them clear the basics before digging deep into the topic.
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
INTRODUCTION TO BIOPHARMACEUTICS , pharmacokinetics, pharmacodynamics and the...krishna keerthi
Biopharmaceutics is a field within the pharmaceutical science that explores the relationship between the formulation of a drug and its pharmacological effects. it delves into how a drug is absorbed, distributed, metabolized, and excreted in the body, aiming to optimize drug delivery for enhanced therapeutic outcomes. this discipline integrates principles of pharmacokinetics , pharmacodynamics and pharmaceutical technology to understand the factors influencing drug bioavailability and efficacy.
Definition of Biopharmaceutics, Application of Biopharmaceutics, Definition of Absorption, Distribution, Metabolism, Excretion, Pharmacokinetics, pharmacodynamics, Bioavailability, Bio-equivalence, Plasma Concentration Vs Time Profile, Pharmacokinetics & pharmacodynamics parameters
“ Bioavailability-
means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action."
Biopharmaceutics Part I
Arba minch unverisity college of health science
department of pharmacy
pharmaceutics and social pharmacy course team for 3rd year pharmacy student
Biopharmaceutics is important for pharmaceutical science:
1. Drug Formulation: Biopharmaceutics provides insights into the development and optimization of drug formulations. It considers factors such as drug solubility, stability, and bioavailability, which are critical for ensuring that a drug can be effectively administered to patients. By understanding the physicochemical properties of drugs, scientists can design appropriate dosage forms such as tablets, capsules, or injectables that deliver the drug in a controlled and efficient manner.
2. Drug Absorption and Bioavailability: Biopharmaceutics investigates how drugs are absorbed into the systemic circulation after administration. It examines processes such as dissolution, permeation, and transport across biological barriers, including the gastrointestinal tract. Understanding drug absorption is essential for predicting drug concentrations at the site of action and determining the bioavailability, which refers to the fraction of the administered drug that reaches the systemic circulation. This knowledge aids in optimizing drug delivery systems and ensuring consistent therapeutic outcomes.
3. Drug-Drug Interactions: Biopharmaceutics explores the potential interactions between drugs and other substances, including food, beverages, and co-administered medications. Certain substances can affect drug absorption, metabolism, or excretion, leading to altered drug concentrations and therapeutic effects. By studying the biopharmaceutical properties of drugs, scientists can identify and manage potential drug interactions, ensuring patient safety and optimizing drug therapy.
4. Pharmacokinetics and Pharmacodynamics: Biopharmaceutics contributes to the understanding of drug pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body). Pharmacokinetics involves the study of drug absorption, distribution, metabolism, and excretion (ADME), while pharmacodynamics focuses on the relationship between drug concentration and the resulting pharmacological effects. Biopharmaceutical principles help determine drug dosages, dosing intervals, and routes of administration to achieve desired therapeutic outcomes while minimizing adverse effects.
Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest
BasicPHARMACOLOGYReview.pptBriefly review information that you have already h...RiyazAhmed21126
Briefly review information that you have already had in your paramedic programs. The purpose of this program is not to teach new concepts of pharmacology.
Announcement about my previous presentations - Thank youAreej Abu Hanieh
ANNOUNCEMENT Thank you for all of you, my followers who sent me messages with a lot of love and appreciations, I finally graduated after 6 years of studying in Birzeit University , In doctor of Pharmacy department I hope all of you benefited from all the presentations posted before Thank you a new PharmD GraduatedAreej ^^
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. PHARMACOKINETICS
• Pharmacokinetics is the science of the kinetics of drug
• absorption,
• distribution, and
• elimination (ie, metabolism and excretion).
• The description of drug distribution and elimination is often termed drug
disposition.
• Characterization of drug disposition is an important prerequisite for
determination or modification of dosing regimens for individuals and groups
of patients.
Phar533 Dr. Abdullah Rabba
2
3. The study of pharmacokinetics
Experimental approach
development of biologic sampling
techniques,
analytical methods for the measurement of
drugs and metabolites,
procedures that facilitate data collection
and manipulation.
Theoretical approach
development of pharmacokinetic
models that predict drug disposition
after drug administration.
(Mathematics and computer
Techniques are heavily utilized)
Phar533 Dr. Abdullah Rabba
3
4. BIOPHARMACEUTICS
• Biopharmaceutics examines the interrelationship of the
• physical/ chemical properties of the drug,
• the dosage form (drug product) in which the drug is given, and
• the route of administration
• on the rate and extent of systemic drug absorption.
Phar533 Dr. Abdullah Rabba
4
6. • biopharmaceutics involves factors that influence:
• (1) the design of the drug product,
• (2) stability of the drug within the drug product,
• (3) the manufacture of the drug product,
• (4) the release of the drug from the drug product,
• (5) the rate of dissolution/release of the drug at the absorption site,
• (6) delivery of drug to the site of action,
Phar533 Dr. Abdullah Rabba
6
7. • The study of biopharmaceutics is based on fundamental scientific principles
and experimental methodology.
• Studies in biopharmaceutics use both in vitro and in vivo methods.
• In vitro methods are procedures employing test apparatus and equipment
without involving laboratory animals or humans.
• In vivo methods are more complex studies involving human subjects or
laboratory animals
Phar533 Dr. Abdullah Rabba
7
8. PHARMACODYNAMICS
• Pharmacodynamics is the study of the biochemical and physiological
effects of drugs on the body; this includes the
• mechanisms of drug action
• relationship between drug concentration and effect.
• A typical example of pharmacodynamics is how a drug interacts
quantitatively with a drug receptor to produce a response (effect).
Phar533 Dr. Abdullah Rabba
8
9. PHARMACODYNAMIC EFFECT
• The pharmacodynamic effect, (the pharmacologic effect), can be therapeutic
and/or cause toxicity.
• For many drugs, the pharmacodynamic effect is dose/drug concentration related;
the higher the dose, the higher drug concentrations in the body and the more
intense the pharmacodynamics effect up to a maximum effect.
• It is desirable that side effects and/or toxicity of drugs occurs at higher drug
concentrations than the drug concentrations needed for the therapeutic effect.
• Unfortunately, unwanted side effects often occur concurrently with the therapeutic
doses.
Phar533 Dr. Abdullah Rabba
9
10. CLINICAL PHARMACOKINETICS
• Clinical pharmacokinetics is the application of pharmacokinetic methods to
drug therapy in patient care.
• It involves a multidisciplinary approach to individually optimized dosing
strategies based on
• the patient’s disease state (e.g. renal, hepatic….)
• and patient-specific considerations (e.g. genetics)
• The study of pharmacokinetic differences of drugs in various population
groups is termed population pharmacokinetics (Sheiner and Ludden, 1992)
Phar533 Dr. Abdullah Rabba
10
11. TDM
• Clinical pharmacokinetics is also applied to therapeutic drug monitoring
(TDM) for very potent drugs, such as those with a narrow therapeutic range,
in order to optimize efficacy and to prevent any adverse toxicity.
• monitoring plasma drug concentrations (e.g., theophylline) or by
• monitoring a specific pharmacodynamic endpoint such as prothrombin clotting
time (e.g., warfarin).
• Pharmacokinetic and drug analysis services necessary for safe drug
monitoring are generally provided by the clinical pharmacokinetic service
(CPKS). Some drugs frequently monitored are the aminoglycosides and
anticonvulsants. Other drugs closely monitored are those used in cancer
chemotherapy, in order to minimize adverse side effects
Phar533 Dr. Abdullah Rabba
11
12. TOXICOKINETICS AND CLINICAL
TOXICOLOGY
• Toxicokinetics is the application of pharmacokinetic principles to the design,
conduct, and interpretation of drug safety evaluation studies (Leal et al,
1993) and in validating dose-related exposure in animals.
• Toxicokinetic data aid in the interpretation of toxicologic findings in animals
and extrapolation of the resulting data to humans. Toxicokinetic studies are
performed in animals during preclinical drug development and may
continue after the drug has been tested in clinical trials.
Phar533 Dr. Abdullah Rabba
12
13. • Clinical toxicology is the study of adverse effects of drugs and toxic
substances (poisons) in the body.
• The pharmacokinetics of a drug in an overmedicated (intoxicated) patient
may be very different from the pharmacokinetics of the same drug given in
lower therapeutic doses.
• At very high doses, the drug concentration in the body may saturate
enzymes involved in the absorption, biotransformation, or active renal
secretion mechanisms, thereby changing the pharmacokinetics from linear
to nonlinear pharmacokinetics.
Phar533 Dr. Abdullah Rabba
13
14. MEASUREMENT OF DRUG
CONCENTRATIONS
• Drug concentrations are an important element in determining individual or
population pharmacokinetics.
• drug concentrations are measured in biologic samples, such as
• milk,
• saliva,
• plasma,
• urine.
• others
Phar533 Dr. Abdullah Rabba
14
15. • Sensitive, accurate, and precise analytical methods are available for the
direct measurement of drugs in biologic matrices.
• chromatographic and mass spectrometric methods are most frequently
employed for drug concentration measurement,
• chromatography separates the drug from other related materials that may
cause assay interference and mass spectrometry allows detection of
molecules or molecule fragments based on their mass-to-charge ratio.
Phar533 Dr. Abdullah Rabba
15
16. SAMPLING OF BIOLOGIC
SPECIMENS
• Invasive methods include sampling
• blood,
• spinal fluid,
• synovial fluid,
• tissue biopsy, or any biologic material that requires parenteral or surgical intervention
in the patient.
• noninvasive methods include sampling of
• urine,
• saliva,
• feces,
• expired air,
• or any biologic material that can be obtained without parenteral or surgical
intervention.
Phar533 Dr. Abdullah Rabba
16
17. DRUG CONCENTRATIONS IN
BLOOD, PLASMA, OR SERUM
• Measurement of drug and metabolite concentrations (levels) in the
• blood,
• serum, or
• plasma
• is the most direct approach to assessing the pharmacokinetics of the drug in
the body.
Phar533 Dr. Abdullah Rabba
17
19. PLASMA DRUG CONCENTRATION–
TIME CURVE
• As the drug reaches the systemic circulation, plasma drug concentrations
will rise up to a maximum if the drug was given by an extravascular route.
• Usually, absorption of a drug is more rapid than elimination.
• As the drug is being absorbed into the systemic circulation, the drug is
distributed to all the tissues in the body and is also simultaneously being
eliminated.
Phar533 Dr. Abdullah Rabba
19
21. • The onset time corresponds to the time required for the drug to reach the
MEC.
• The intensity of the pharmacologic effect is proportional to the number of
drug receptors occupied, which is reflected in the observation that higher
plasma drug concentrations produce a greater pharmacologic response,
up to a maximum.
• The duration of drug action is the difference between the onset time and
the time for the drug to decline back to the MEC.
Phar533 Dr. Abdullah Rabba
21
22. • The therapeutic window is the concentrations between the MEC and the MTC.
• Drugs with a wide therapeutic window are generally considered safer than drugs with a
narrow therapeutic window.
• Sometimes the term therapeutic index is used. This term refers to the ratio between the
toxic and therapeutic doses.
Phar533 Dr. Abdullah Rabba
22
24. • peak plasma level (Cmax), is related to the dose, the rate constant for
absorption, and the elimination constant of the drug
• time for peak plasma level (Tmax) is the time of maximum drug concentration
in the plasma and is a rough marker of average rate of drug absorption
• area under the curve, or AUC The AUC is related to the amount of drug
absorbed systemically.
Phar533 Dr. Abdullah Rabba
24
25. PHARMACOKINETIC MODELS
• Drugs are in a dynamic state within the body as they
• move between tissues and fluids,
• bind with plasma or cellular components, or
• are metabolized.
• The biologic nature of drug distribution and disposition is complex, and drug events
often happen simultaneously.
• Such factors must be considered when designing drug therapy regimens.
• The inherent and infinite complexity of these events requires the use of
mathematical models and statistics to estimate drug dosing and to predict the time
course of drug efficacy for a given dose.
Phar533 Dr. Abdullah Rabba
25
26. PHARMACOKINETIC MODELS
• A model is a hypothesis using mathematical terms to describe quantitative
relationships concisely.
• The model predicts (estimates) certain kinetic parameters by the
proper selection and development of mathematical function(s) that
fit kinetic variables (experimental data).
• A pharmacokinetic function relates an independent variable to a
dependent variable.
Phar533 Dr. Abdullah Rabba
26
27. • For example, a pharmacokinetic model may predict the drug
concentration in the liver 1 hour after an oral administration of a 20-mg dose.
• The independent variable is time and the dependent variable is the drug
concentration in the liver.
• Such mathematical models can be devised to simulate the rate processes of
drug absorption, distribution, and elimination to describe and predict drug
concentrations in the body as a function of time.
Phar533 Dr. Abdullah Rabba
27
28. • Simplifying assumptions are made in pharmacokinetic models to describe a
complex biologic system concerning the movement of drugs within the
body.
• For example, most pharmacokinetic models assume that the plasma drug
concentration reflects drug concentrations globally within the body.
Phar533 Dr. Abdullah Rabba
28
29. • Pharmacokinetic models are used to:
1. Predict plasma, tissue, and urine drug levels with any dosage regimen
2. Calculate the optimum dosage regimen for each patient individually
3. Estimate the possible accumulation of drugs and/or metabolites
4. Correlate drug concentrations with pharmacologic or toxicologic activity
5. Evaluate differences in the rate or extent of availability between formulations
(bioequivalence)
6. Describe how changes in physiology or disease affect the absorption,
distribution, or elimination of the drug
7. Explain drug interactions
Phar533 Dr. Abdullah Rabba
29
30. PHARMACOKINETIC MODELS
A model may be:
1. Empirically based:
Simply interpolates the data and allows an empirical formula to
estimate drug level over time (justified when limited information is
available).
Empirical models are practical but not very useful in explaining the
mechanism of the actual process by which the drug is absorbed,
distributed, and eliminated in the body.
Phar533 Dr. Abdullah Rabba
30
31. 2. Physiologically based models:
Requires tissue sampling.
Requires monitoring organ blood flow.
Used in describing drug distribution in animals (tissue samples are
easily available for assay)
Has limitations to its use in humans.
Phar533 Dr. Abdullah Rabba
31
32. 3. Compartmentally based models:
Very simple and useful tool in pharmaco-kinetics.
For example, assume a drug is given by intravenous injection and
that the drug dissolves (distributes) rapidly in the body fluids.
Phar533 Dr. Abdullah Rabba
32
33. COMPARTMENTALLY BASED
MODELS:
• A model that can describe this situation is a tank containing a volume of
fluid that is rapidly equilibrated with the drug.
• The concentration of the drug in the tank after a given dose is governed by
two parameters:
(1) the fluid volume of the tank that will dilute the drug.
(2) the elimination rate of drug per unit of time.
Phar533 Dr. Abdullah Rabba
33
34. COMPARTMENTALLY BASED
MODELS:
Because a model is based on a hypothesis, a certain degree of caution is
necessary when relying totally on the pharmacokinetic model to predict
drug action.
For some drugs, plasma drug concentrations are not useful in predicting
drug activity.
For other drugs, an individual's genetic differences, disease state, and the
compensatory response of the body may modify the response of a drug.
Phar533 Dr. Abdullah Rabba
34
35. • A compartment is not a real physiologic or anatomic region but is
considered as a tissue or group of tissues that have similar blood flow
and drug affinity.
• Within each compartment, the drug is considered to be uniformly
distributed.
• Mixing of the drug within a compartment is rapid and homogeneous
and is considered to be "well stirred,"
• so that the drug concentration represents an average concentration,
and each drug molecule has an equal probability of leaving the
compartment.
Phar533 Dr. Abdullah Rabba
35
36. Rate constants are used to represent the overall rate processes of drug
entry into and exit from the compartment.
The model is an open system because drug can be eliminated from the
system.
A compartmental model provides a simple way of grouping all the tissues
into one or more compartments where drugs move to and from the central
or plasma compartment.
Phar533 Dr. Abdullah Rabba
36
37. MAMMILLARY MODEL
• A compartmental model provides a simple way of grouping all the tissues into one
or more compartments where drugs move to and from the central or plasma
compartment.
The mammillary model is the most common compartment model used in
pharmacokinetics.
The mammillary model is a strongly connected system, because one can estimate
the amount of drug in any compartment of the system after drug is introduced into
a given compartment.
The mammillary model consist of one or more compartments around a central
compartment like satellites.
Phar533 Dr. Abdullah Rabba
37
38. MAMMILLARY MODELS
One-compartment model:
Drug is both added to and eliminated from a central compartment.
The central compartment is assigned to represent plasma and highly perfused
tissues that rapidly equilibrate with drug.
When an intravenous dose of drug is given, the drug enters directly into the central
compartment.
Elimination of drug occurs from the central compartment because the organs
involved in drug elimination, primarily kidney and liver, are well-perfused tissues.
Phar533 Dr. Abdullah Rabba
38
40. MAMMILLARY MODELS
Two-compartment model:
drug can move between the central or plasma compartment to and from
the tissue compartment.
The total amount of drug in the body is simply the sum of drug present in
the central compartment plus the drug present in the tissue compartment.
Phar533 Dr. Abdullah Rabba
40
42. PHYSIOLOGIC PHARMACOKINETIC
MODEL (FLOW MODEL)
The model would potentially predict realistic tissue drug concentrations,
which the two-compartment model fails to do.
Much of the information required for adequately describing a physiologic
pharmacokinetic model are experimentally difficult to obtain.
In spite of this limitation, the physiologic pharmacokinetic model does
provide much better insight into how physiologic factors may change drug
distribution from one animal species to another.
Phar533 Dr. Abdullah Rabba
42