PHARMACOKINETICS

Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion . A fundamental concept in pharmacokinetics is drug clearance, that is, elimination of drugs from the body, analogous to the concept of creatinine clearance. In clinical practice, clearance of a drug is rarely measured directly but is calculated as either of the following:

AUC, the area under the curve, represents the total drug exposure integrated over time and is an important parameter for both pharmacokinetic and pharmacodynamic analyses. As indicated in equation 1, the clearance is simply the ratio of the dose to the AUC, so that the higher the AUC for a given dose, the lower the clearance. If a drug is administered by continuous infusion and a steady state is achieved, the clearance can be estimated from a single measurement of the plasma drug concentration (Css) as in equation 2.

Clearance can conceptually be considered to be a function of both distribution and elimination. In the simplest pharmacokinetic model,

V is the volume of distribution, and K is the elimination constant. V is the volume of fluid in which the dose is initially diluted, and thus the higher the V, the lower the initial concentration. K is the elimination constant, which is inversely proportional to the half-life, the period of time that must elapse to reach a 50% decrease in plasma concentration. When the half-life is short, K is high and plasma concentrations decline rapidly. Thus both a high V and a high K result in relatively low plasma concentrations and a high clearance.