Preparation of mean drug concentration-time curves in plasma. A study on the frequency distribution of pharmacokinetic parameters.

Abstract

A study on the frequency distribution of various pharmacokinetic parameters was conducted using pharmacokinetic data based on human blood samples obtained after administration of 3 cephalosporin derivatives [cefsulodin, cefotiam and cefmenoxime]. Pharmacokinetic parameters ka [absorption rate constant], ke [elimination rate constant], V [apparent volume of distribution], .alpha., .beta. [half-lives], k12, k21 [transfer rate constants], V1 [pharmacokinetic volume of central compartment] Vd [apparent volume of distribution of .beta.-phase] and Cl [total body clearance] followed lognormal distribution curves rather than normal distribution curves. In the case of a one-compartment open model, mean plasma concentration-time curves could be prepared more precisely by use of the geometrical mean values of V, kc and ka. In the case of a 2-compartment open model, the use of the geometrical mean values of V1, .alpha., .beta. and ke rather than those of V1, k12, k21 and ke was considered to be preferable in view of the reliability of the rate constants .alpha., .beta., k12 and k21.