This document provides an overview of how pharmacokinetics principles can be applied in drug development and clinical practice. It discusses how pharmacokinetics helps in designing new drugs with improved efficacy and safety, optimizing formulations, and regulating drug dosing. Factors like absorption, distribution, metabolism and excretion that influence drug behavior in the body are considered. The effects of lipophilicity and solubility on absorption and ways to modify pharmacokinetic properties like half-life are summarized. References on biopharmaceutics and pharmacokinetics textbooks are also provided.
factors affecting protein drug binding
significance of protein binding
drug related factors
protein related factors
drug interactions
patient related factors
Definition of drug interaction ,types and factors contributing to drug interactions. Mechanisms of Drug Interaction. Absorption, Distribution, Metabolism and Excretion interactions with examples(ADME INTERACTIONS).Prevention of drug interaction.
Drug-drug interactions(DDI) are one of the commonest causes of medication error, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. Drug interactions represent factors of uncertainty in many therapeutic situations. Drug–drug interactions can cause profound clinical effects, either by reducing therapeutic efficacy or enhancing toxicity of drugs. With an increasing frequency in polypharmacy, DDIs are one of the major causes for drug withdrawal from the market. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. Although DDIs can result in alterations of either drug pharmacokinetics (PK), pharmacodynamics(PD), or both, it is the pharmacokinetic drug interactions that is clinically significant. PK drug interactions, typically characterized by alterations of plasma concentration–time profiles, could be attributed to changes in processes of absorption, distribution, metabolism, and excretion of a drug substance mediated by another drug when they are given concomitantly. In this review we mainly focused on the pharmacokinetic drug interactions with various drug examples and their mechanism of drug interactions that are clinically significant.
factors affecting protein drug binding
significance of protein binding
drug related factors
protein related factors
drug interactions
patient related factors
Definition of drug interaction ,types and factors contributing to drug interactions. Mechanisms of Drug Interaction. Absorption, Distribution, Metabolism and Excretion interactions with examples(ADME INTERACTIONS).Prevention of drug interaction.
Drug-drug interactions(DDI) are one of the commonest causes of medication error, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. Drug interactions represent factors of uncertainty in many therapeutic situations. Drug–drug interactions can cause profound clinical effects, either by reducing therapeutic efficacy or enhancing toxicity of drugs. With an increasing frequency in polypharmacy, DDIs are one of the major causes for drug withdrawal from the market. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. Although DDIs can result in alterations of either drug pharmacokinetics (PK), pharmacodynamics(PD), or both, it is the pharmacokinetic drug interactions that is clinically significant. PK drug interactions, typically characterized by alterations of plasma concentration–time profiles, could be attributed to changes in processes of absorption, distribution, metabolism, and excretion of a drug substance mediated by another drug when they are given concomitantly. In this review we mainly focused on the pharmacokinetic drug interactions with various drug examples and their mechanism of drug interactions that are clinically significant.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
Pharmacokinetics and pharmacodynamics of Biotechnological drugs-SnehalTidke
Pharmacokinetics and pharmacodynamics of biotechnological drugs along with appliations- Proteins and peptides, monoclonal antibodies, oligonucleotides, gene therapy and vaccines
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
Pharmacokinetics and pharmacodynamics of Biotechnological drugs-SnehalTidke
Pharmacokinetics and pharmacodynamics of biotechnological drugs along with appliations- Proteins and peptides, monoclonal antibodies, oligonucleotides, gene therapy and vaccines
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Fundamental concept of modified drug releaseAbhinayJha3
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
SELECTION OF DRUG CANDIDATE FOR ORAL SUSTAINED RELEASE SYSTEMS, BIOPHARMACEUTICAL CLASSIFICATION SYSTEM.
Fundamental concept of modified drug releaseAbhinayJha3
BIOPHARMACEUTICAL CLASSIFICATION SYSTEM
Different Terminologies used in a modified release
1. Sustained release
2. Delayed release
3. Prolonged release
4. Extended-release
5. Controlled release
6. Site-specific targeting and receptor targeting
1. PREPARED BY:- GUIDE BY:-
PATEL PARTH Mr. V.M.PATEL
M.PHARM SEM-1
DEPARTMENT OF QUALITY ASSURANCE
A.P.M.C COLLEGE OF PHARMACEUTICAL SCIENCE &
RESEARCH,
HIMMATNAGAR.
2. Design and development of new drugs with greatly improved
therapeutic effectiveness and fewer or no toxic effects
Design and development of an optimum formulation for better
use of the drug
Design and development of controlled/targeted release
formulation
Select the appropriate route for drug administration
3. Select the right drug for a particular illness
Predict and explain drug-food and drug-drug interactions
Design an appropriate multiple dosage regimen
Therapeutic drug monitoring in individual patients
Dosage adjustments in situations of altered physiology
and drug interactions
4. To understand process of absorption, distribution and
elimination of drug , which affects onset and intensity of
biological response.
To access plasma drug concentration response to given dose
which is now considered as more appropriate parameter then
intrinsic pharmacological activity .
In design and utilization of in vitro model system that can
evaluate dissolution characteristics of new compound
formulated as new drug formulations and establish meaningful
in vivo in vitro correlation ship.
In design and development of new drug and their appropriate
dosage regimen.
In safe and effective management of patients by improving
drug therapy.
5. To understand concept of bioavailability which has been used to
evaluate and monitor in vivo performance of new dosage forms
and generic formulations.
To carry out bioavailability and bioequivalence studies.
We can use pharmacokinetic principles in the development of
various NDDS.
e.g. The drug with short half life about 2-6 h can be
formulated as controlled release drugs by using polymers .
The lower bioavailability of the drugs can be increased by
using several components like β – cyclodextrin
List of drug carriers in NDDS :-
Nanosomes, Liposomes, Niosomes, Proniosomes, vesicular
drug delivery system, Cubisomes, Aquasomes,
Pharmacosomes,Nanoparticle, Nanosphere, Microsphere,
Microparticle, Transferosomes, Micro emulsion,
Nanosuspension, Dendrimers, Micelles, Dendrosomes.
6. Many drugs are investigated now a days and the estimation of
their activity and pharmacokinetics properties are important
for knowing the ADME of that particular drug . By
understanding the mechanism of disease the drug design is
done .The drug design is based on the mechanism of the
particular disease. Some newly discovered drugs that shows
very high activity in in vitro but in in vivo that drug not shows
high activity or show high toxic activity. This toxic nature of
the drug in in vivo can be explained by studying the
pharmacokinetics properties that is the formation of reactive
metabolites.
Some newly invented drugs showing undesirable pk properties
such as too long or too short t 1/2 , poor absorption and
extensive first pass metabolism .
7. Two physicochemical factors that effect the both extent and
rate of absorption are lipophilicity and solubility .
Increase in the lipophilic nature of drug results in increased in
oral absorption .
e.g. Biophosphonates drug with poor lipophilicity will be
poorly absorbed after oral administration . Absorption of
the barbiturates compounds increased with increasing
lipophilicity.
Higher the lipophilicity of a drug the higher its permeability
and the greater its metabolic clearance due to first pass effect.
8. Solubility is also an important determinant in drug absorption.
e.g. HIV protease inhibitors are basically lipophilic and
poorly soluble resulting in poor bioavailability. The
solubility of the HIV protease inhibitors can increased
by incorporating a basic amine in to the back bone of this
series.
Pro drugs are developed to improve oral absorption .
e.g. Pivampicillin, Becampicillin are the pro drugs of
Ampicillin.
9. Lipophilicity of the drug affects the distribution. Higher the
lipophilicity of a drug the stronger its binding to protein & the
greater its distribution.
e.g. Thiopental & polychlorinated insecticides. These drugs
are highly distributed and accumulate in adipose
tissue.
10. Determination of metabolic pathways
Study of drug metabolic pathways are useful for determining
the nature of metabolites and used for toxicity studies.
Isolation & cultured hepatocytes are also often used as in-vitro
models for identifying metabolic pathways of drug.
e.g. The major metabolic pathways of indinavir in human have
been identified as,
o Glucaronidation at the pyridine nitrogen to yield a quaternary
ammonium conjugate
o Pyridine n-oxidation
o Para –hydroxylation of the phenyl methyl group
o 3-hydroxylation of the chain
o N- depyridomethylation
11. Administration of a drug with a short half life requires frequent
dosing and often results in patient incompliance. Half life
determined by distribution & elimination. The prolongation of
half life can be achieved by increasing the volume of
distribution & decreasing the clearance. Latter appear to be
easier i.e. to modify the chemical structure to slow down a drug
clearance than to increase its volume of distribution.
e.g. The addition of an alkyl amine side chain linked to the
dihydropyridine 2-methyl group yield amlodipine with a lower
clearance which has an improved oral bioavailability and
plasma half life without loss of antihypertensive activity.
12. Biopharmaceutics & clinical pharmacokinetics by Milo
Gilbaldi 4th edition , Philadelphia lea & Febiger 1991
Biopharmaceutics & pharmacokinetics a treatise D.M.
Brahmankar & Sunil b. Jaiswal ,Vallabh Prakashan
Pitampura, Delhi
Text book of Biopharmaceutics & pharmacokinetics by
Dr.shobha rani R.Hiremath, prism books Pvt
Ltd,bangalore,2002