Pharmacokinetic parameters: which are necessary to define a drug substance?

Abstract

Pharmacokinetics describe what the body does to the drug, as opposed to pharmacodynamics which describe what the drug does to the body. Pharmacokinetic information is required to optimize the pharmacodynamic response. The primary pharmacokinetic disposition parameter is clearance. Knowledge of this value and its major constituent parts, i.e. fractional renal and hepatic elimination, allows the clinician to prescribe the correct dosage regimen to obtain a mean therapeutic concentration and to predict the effects of various disease states. The other primary disposition parameter, volume of distribution at steady-state, may also vary with changes in physiologic and pathologic conditions. Both clearance and volume of distribution as well as the correlation of concentration measurements with pharmacodynamics would be expected to vary with changes in plasma protein binding. Although plasma concentration measurements are usually easiest to perform, interpretation of parameters in physiologic terms requires blood concentration, so the blood/plasma partition parameter should be determined. Although half-life is a composite parameter reflecting changes in both clearance and volume of distribution, it is a value which defines the maximum and minimum blood concentrations obtained for a particular dosage regimen, important quantities in defining the pharmacodynamic response. The major pharmacokinetic input parameter is the extent of availability as a function of route of administration. This parameter, as well as all of the disposition parameters discussed above, may be determined without designating a particular pharmacokinetic model. Only the rate of availability requires a model, although peak time and peak concentration are reasonable noncompartmental substitutes.