INTRODUCTION TO PHARMACOKINETICS

PHARMACOKINETICS

It is the science of the kinetics of drug absorption, distribution & elimination.

PK of a drug depends on patient- related factors as well as on the drug’s chemical properties.

Study involves experimental & theoretical approaches

Experimental aspect involves the development of biological sampling techniques, analytical methods and procedures that facilitate data collection.

Theoretical aspect involves development of pharmacokinetic models.

Statistical methods.

Mathematics & computer techniques.

CLINICAL PHARMACOKINETICS

Application of pharmacokinetic methods to drug therapy.

Multidisciplinary approaches to individually optimized dosing strategies based on the patient’s disease state & patient-specific consideration.

Population pharmacokinetics

Study of pharmacokinetic difference of drugs in various population groups.

PHARMACODYNAMICS

It refers to the relationship b/w the drug concentration at the site of action (receptor) & pharmacologic response, including biochemical & physiologic effects that influence the interaction of drug with the receptor.

TOXICOKINETICS

It is the rate at which a chemical will enter the body & what happens to it once it is in the body.

CLINICAL TOXICOLOGY

• It is the study of adverse effects of drugs & toxic substances (poisons) in the body.

• It is a subspecialty of medicine.

• Practiced by toxicologists.

• Used in emergency medicine, occupational medicine &pediatrics.

MEASUREMENT OF DRUG CONCENTRATION

• SAMPLING OF BIOLOGIC SPECIMENS

INVASIVE METHODS include sampling blood, spinal fluid, synovial fluid, tissue biopsy or biologic material that requires parenteral or surgical intervention in the patient.

NON-INVASIVE METHODS include sampling of urine, saliva, feces, expired air or any biologic materials that can be obtained without parenteral or surgical intervention.

1.Drug concentration in blood, plasma, or serum.

• Most direct approach

• In general serum or plasma is most commonly used for drug measurement.

• Change in drug concentration in plasma will reflect changes in tissue drug concentration under dynamic equillibrium.

Plasma Level – Time Curve

• Concentration of drug in each plasma sample against corresponding time at which the plasma sample was removed.

• Onset time

• Duration of action

• Peak plasma level

• AUC

Drug Concentration In Tissues

• Tissue biopsies used for verification of malignancy.

• Small sample is removed, hence measurement of drug concentration difficult.

• Used to ascertain if the drug reached the tissue & reached the proper concentration within the tissues.

Drug Concentrations in Urine & Feces

• It is an indirect method to ascertain the bioavailability of a drug.

• The rate & extent of drug excreted in urine reflects the rate & extent of systemic drug absorption.

• Measurement of drug in feces may reflect drug that has not been absorbed after an oral dose or may reflect drug that has been expelled by biliary secretion after systemic absorption.

• Used for TDM because only free drug diffuse into the saliva, saliva drug levels tend to approximate free drug rather than total plasma drug conc.

• The ratio of saliva/plasma drug concentration ratio less than 1 for many drugs.

• It is influenced by pKa of a drug & pH of the saliva.

Drug Concentration in Saliva

Significance of measuring plasma drug concentration :

• Estimation of the plasma drug level is an appropriate method of monitoring the course of therapy.

• Allows for the adjustment of the drug dosage in order to individualize & optimize therapeutic drug regimen.