Dr.

Ajay Chavan
Dept. of Rasashastra

Contents
Introduction Objective Definition Description of ADME Disciplines Models Application Own research view Research article Summary Conclusion
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Introduction
Greek pharmakon "drug" and kinetikos to do with motion" It deals with the rates of movement of drug and its metabolite in the body and forces acting on the process. Rates of movement of drugs will explain with the help of suitable Mathematical Model.
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Contd«
Concentration of a drug in plasma or any physiological fluid such as urine, saliva, milk, etc., is determined with respect to time following its administration. Based on the hypothesis that the action of a drug requires presence of a certain concentration in the target tissue.
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Objective
Brief overview to understand regarding Pharmacokinetic action

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Definition
Pharmacokinetics is the study of what the body does to a drug. The quantitative study of the Absorption, Distribution, Metabolism and Excretion of drugs and their metabolites.
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Absorption
It is an amount of drug that enters in blood after it s administration in body. Factor affecting absorption: 1) Nature of Drug  Fat-Soluble drugs are maximally absorbed  Water-Soluble drugs are less absorbed

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Contd«
2) Route Parenterally: Oral  Intravenous: Sublingual  Intramuscular: Rectal  Subcutaneous: Transcutaneous Inhalation: Absorption through mucous membranes Topical
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Distribution
An amount of drug that reaches to cell, after absorption. After absorption into the systemic circulation, drugs are distributed throughout the body. Highly perfused organs such as brain, hearts, lungs, liver and kidneys receive most of the drug soon after injection.
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Processes of Distribution 
It involves two steps: 1. Permeation of free or unbounded drug present in blood through the capillary wall and entry into ECF. 2. Permeation of drug present in ECF through membrane of tissue cells and into the ICF.
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Factors Affecting Drug Distribution
1.Tissue permeability. 2.Organ or tissue size and perfusion rate. 3.Binding of drugs to tissue components. 4.Miscellaneous
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Metabolism
The irreversible transformation of parent compounds into daughter metabolites. A mechanism by which, mostly liver alter chemical structure of drug. It become non-toxic, water soluble and easily excrete outside body through urine or faeces
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Contd«
By this, mostly fat-soluble drug are convert into water-soluble while water-soluble mostly remain unchanged.

Liver can do metabolism by Conjugation, Reduction, Hydroxylation etc
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Excretion
The elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.

Water soluble drug is excreted outside mostly through urine or faeces.
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Contd«
Excreted drug may changes color and nature of urine or faeces.

Some drug also excreted through sweating, lacrymation, breast milk
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Disciplines
1. Clinical Pharmacokinetics 2. Population Pharmacokinetics 3. Toxicokinetics 4. Clinical Toxicology
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Clinical Pharmacokinetics
Is the application of pharmacokinetic

methods to drug therapy. It involves a multidisciplinary approach to individually optimized dosing strategies based on the patient's disease state and patientspecific considerations.
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Population Pharmacokinetics
Use in the drug development process to help identify differences in drug safety and efficacy among population subgroups.

The study of pharmacokinetic differences of drugs in various population groups is termed as population pharmacokinetics.
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Contd«
Age, gender, genetic, and ethnic differences can also result in pharmacokinetic differences that may affect the outcome of drug therapy.

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Toxicokinetics
Is the application of pharmacokinetic principles to the design, conduct, and interpretation of drug safety evaluation studies.

Toxicokinetics data aids in the interpretation of toxicologic findings in animals and extrapolation of the resulting data to humans.
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Clinical Toxicology

Is the study of adverse effects of drugs and toxic substances (poisons) in the body

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Pharmacokinetic Models
Various mathematical models are useful in the development of equations to describe drug concentrations in the body. Drug concentrations are dependent on time, the two variables drug concentration and time are called dependent and independent variables respectively
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Contd«
Useful in : Characterize the behavior of drug in patient. Predicting conc. of drug in various body fluids with dosage regimen. Calculating optimum dosage regimen for individual patient. Evaluating bioequivalence between different formulation. Explaining drug interaction.
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Contd«
Pharmacokinetic models are divided into 1. Compartment models 2. Physiological pharmacokinetic model (flow model) 3. Non Compartmental Pharmacokinetics model 4. Non linear Pharmacokinetics model
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Compartmental Model
Models are based on the concept that the body may be viewed as a series of compartments in which the drug is distributed. It divided into 1. One Compartment Models 2. Two Compartment Models
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Contd«
One Compartment Models: Entire body is considered as one unit Drug is administered into the compartment and distributed throughout the compartment (the body) instantaneously
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Contd«
Two Compartment Models: In this model, drug is administered into the central compartment and then there is a time lag due to slower distribution into other tissues and organs. These other organs are represented by the peripheral compartment
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Physiological Models
An alternate method of building a pharmacokinetic profile of a drug in the body is to utilize anatomic and physiological information. It decide whether drug distribution into a particular tissue is by perfusion rate or membrane transport. The other parameters like venous concentration and the partition coefficient
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Noncompartmental
It is highly dependent on estimation of total drug exposure.

Total drug exposure is most often estimated by area under the curve (AUC) methods.
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Nonlinear Model
Concept of linear Pharmacokinetics is the concentrations achieved are proportional to the dose given.

For example, a doubling of the dose will produce
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concentration.

Contd«
For some drugs an increase in dose may produce a concentration much greater than expected. For example, increases in dosage of the antiepileptic agent Phenytoin above approximately 300 mg daily usually produce a greater than expected increase in blood concentrations.
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Theoretical depiction of plasma concentrations following either an intravenous bolus dose immediately followed by initiation of a continuous intravenous infusion or initiation of a continuous intravenous infusion only.

Applications
To understand process of ADME after administration of drug, which affects onset and intensity of biological response. 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 invitro correlationship.
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Contd«
To carry out bioavailability and bioequivalence studies. In design and development of new drug and their appropriate dosage regimen. Pharmacokinetic principles can used in the development micro spheres and Nanoparticles.
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Own Research View
PK action for the Ayurvedic drugs can be detect by parameters like Rasa, Guna, Avstha Paka, Vipaka (Nistha Paka). Rasa is identified when drug come in contact with tongue which is after Absorption. Guna is identified by rate of Distribution in body
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Contd«
Vipaka (Avastha Paka) of drug determine by Metabolism in systemic circulation. The Excretion of drug through body is one of the criteria asses to Vipaka (Nistha Paka). Virya & Prabhava can determine by Pharmaco Dynamics of drug.
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Research Article
Pharmacokinetics of High-Dose Oral Thiamine Hydrochloride In Healthy Subjects.
Howard A Smithline, Michael Donnino, David J. Greenblatt

Conclusion
It shows that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process.
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Summary
Definition of PK Description of ADME Disciplines like Population PK, Clinical PK etc. Mathematical Models- compartment model, Physiological model etc. Application of PK
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Conclusion
It explain the total clearance of drug and its steady state plasma concentration during continues administration. It very useful in drug development and dose fixation. We must think about application of PK for Ayurvedic drugs.
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References
Rang and Dale s Pharmacology Text Book of Pharmacology Tripathi Text Book of Pharmacology Satoskar Basic Pharmacokinetics Sunil Jambhekar & Philip Breen http://www.biomedcentral.com/14726904/12/4 Internet
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