Pharmacokinetics

Pharmacokinetics describes the concentrations of drug in the body over time

Mathematical representation is used to describe absorption, distribution, metabolism, and excretion

Related to effects of drugs on the body, or pharmacodynamics

Information is used to perform dosage calculations

Absorption

Bioavailability is affected by the route of administration and must be factored into dose calculations

Major factors affecting bioavailability with oral drugs include:

Reversible movement from blood to body tissues

Extent depends on:

apparent volume of fluid in which a drug is distributed
assumes equal partioning throughout body; ie plasma concentration = that of rest of body
as Vd remains contstant for a given drug, dose can be calculated to acheive a desired concentration

Vd = Q / Cp

A large Vd implies retention in tissues outside of plasma, while a small Vd implies primary plasma retention

Some tissues have more/less affinity for a given agent

Binding to plasma proteins such as albumin reduces the amount of drug available, but acts as a reservoir

metabolism of any given drug can vary up to 50-fold in a population, based on:

creating or unmasking of small polar/reactive groups, ie -OH, -SH, -NH₂
cytochrome P450 (CYP) families 1,2,3responsible
- broad substrate range; low individual specificity
- expression varies amongst individuals
- can be induced or inhibited by drugs and diet compounds
  - most common cause of ADRs

conjugation of larger polar groups to small reactive functional groups, ie glucuronic acid, sulfate, glutathione, acetate

Elinimation half-life is independent of dose

Kidney is most important route for drug and metabolites, with active secretion taking place

Liver: bile

Other:sweat, tears, reproductive fluids, milk, lung