data

1. Pharmacokinetics of Single and Multiple Dose
PRESENTATION BY: AZKA MARJAN

2. Pharmacokinetics
• The term “Pharmacokinetics” mean the quantitative study of absorption,
distribution and elimination (metabolism + excretion) of drugs.
• Simply it can be defined as the effect of body or effect of physiological processes
of body onto the drug. These barriers that a drug faces after administration are
known as pharmacokinetic processes.
• The main principles are ADME.
1. Absorption
• The transfer of drug molecules from the site of administration or from the site of
drug release into the systemic circulation either through passive diffusion or active
transport is known as absorption of drug.

3. 2. Distribution
Tissue differences in rates of uptake of drugs.
Blood flow: distribution occurs most rapidly into tissues with high blood flow (lungs,
kidneys, liver, brain) and least rapidly in tissues with low flow (fat).
Capillary permeability: permeability of capillaries is tissue dependent; distribution rates
relatively slower into CNS because of tight junction between capillary endothelial cells,
insignificant aqueous membrane pores, juxtaposed glial cells around endothelium and
efflux transporters in vascular endothelium ("blood-brain barrier"); capillaries of liver
and kidney more porous.

4. Plasma protein binding
• Many drugs reversibly bind to albumin, α1-acid glycoprotein or other proteins in
plasma
• Extent of binding dependent on affinity, number of binding sites, and drug
concentrations
• Drug bound to albumin is not filtered by renal glomerulus but may be cleared by
proximal renal tubule and liver
• Binding reduces free drug available for distribution into tissue
• Many drug interactions based on displacement from binding sites.

5. 3. Metabolism
• It covers the metabolism and excretion of the drug from the body.
• Metabolism ads to the inactivation of drug molecules by the action of specific enzymes and
converting them into complex entities or water soluble moieties which are then excreted from
body through urine, feces, milk or sometimes saliva.
4. Elimination
• Elimination is mainly associated with the irreversible removal of drug from the body.
Total Clearance (ClT)
• Volume of plasma completely cleared of drug per unit time by all routes and mechanisms.
Cltotal = Cl renal + Cl hepatic

6. Excretion
• Elimination of drug by excretion unchanged in body fluid or breath.
• Routes of excretion
Urine: quantitatively most important excretory route for nonvolatile drugs
and their metabolites; excretion rate depends on rate of glomerular filtration
(drug not bound to plasma proteins), proximal tubular active secretion, and
passive reabsorption

7. Pharmacokinetic studies
STANDARD PHARMACOKINETIC STUDY
A standard pharmacokinetic study is the
conventional method for evaluating the
pharmacokinetics of a drug in healthy human
subjects or highly selected patients.
For example, determination of bioavailability of drug
in plasma or estimation of various parameters e.g.
Cmax, Tmax, Vd, elimination rate constant etc.
Subjects are given a single dose or repeated doses of
an investigational drug.
No. of subjects taken are small but no. of samples
taken from each subject are large
POPULATION PHARMACOKINETIC STUDY
Population pharmacokinetics is the study of the
sources and correlation of variability in drug
concentrations among individuals who are the target
patient population receiving clinically relevant doses
of a drug of interest.
For example, steady-state concentrations of drugs
eliminated mostly by the kidney are usually greater in
patients suffering from renal failure than they are in
patients with normal renal function who receive the
same drug dosage.
Usually a large number of subjects participate in the
study, while the number of samples collected from
each subject can be small.

8. Pharmacokinetic studies
STANDARD PHARMACOKINETIC STUDY POPULATION PHARMACOKINETIC STUDY
This approach is considered suitable for special
populations such as the elderly and children.
These studies involve two approaches;
The Two-Stage Approach
The Nonlinear Mixed-Effects Modeling Approach
Usually, the pharmacokinetic characteristics of a
drug are examined by the "standard
pharmacokinetic studies.
These studies can be of two types.
Single dose studies and
Multiple dose studies