Pharmacokinetics Pharmacodynamics Pharmacokinetics Movement of drugs in the

Pharmacokinetics & Pharmacodynamics

Pharmacokinetics • Movement of drugs in the body or effect of body on drugs • Four Processes • • Absorption Distribution Metabolism Excretion

Absorption • Depends on intravascular and extravascular route of drug administration • It entails transport of drug across small intestinal epithelial cell membrane. • Transport through membrane also important in other process of pharmacokinetics

Transport through Membrane • Diffusion through paracellular space • Through lipid bilayer • Facilitated diffusion (Carrier mediated transport) • Active transport (Carrier mediated with energy requirement) • Most drug cross membrane through passive means (Lipid bilayer)

Diffusion through Lipid • Factors affecting the transport through lipid can be summarized using Ficks law; C 1 – C 2 x A. PC/T • Permeability Coefficient depends on; Partition coefficient and diffusivity • Part Coefficient depends on pka of drug, p. H of absorption site and blood. They determine degree of ionization

Diffusion through Lipid • Factor related to drug include presence of functional group, mol wgt. of drug. • Based on degree of ionization effective absorption can be det. using H-H equation for weak acid or base. • Assuming p. H of stomach is 1. 4 and Aspirin p. Ka is 3. 4, det. Efficiency of aspirin absorption. • Other factors affecting absorption include; perfusion rate, gastric emptying, Competing reactions and formulation of drug.

Absorption • Absorption can also determine bioavailability • But not the major determinant when drug is absorbed through small intestine. • Bioavailability can be referred to as fractional extent of drug dose carried by the blood to site of action. • Det. Bioavailability if 50% of drug dose is lost at each step of drug between absorption and reaching systemic circulation • Absolute bioavailability in I. V.

p. Ka of Drugs

Route of Drug Admin.

Drug Distribution • The process by which a drug reversibly leaves the blood stream and enters the interstitium (extracellular fluid) and get into the cells or tissues. • The drugs are present in free or bound form and different processes or mechanisms affect their distribution. Compartments for Distribution: • Plasma • Interstitial fluid • Intracellular fluid • Transcellular fluid

Factors Affecting Drug Distribution • Lipid Solubility • Molecular size • Degree of Ionization • Free and Bound Form • Drug Reservoirs • Vascularity • Barrier; placenta, BBB (Pharmacological sanctuaries) • Volume of Distribution • Removal rate and tissue binding