Prediction of the volumes of distribution of basic drugs in humans based on data from animals

Abstract

The apparent volume of distribution-after distribution equilibrium and the ratio of distributive tissue volume to the unbound fraction in the tissue (V_T/fu_T)of 10 weak basic drugs, i.e., chlorpromazine, imipramine, propranolol, disopyramide, lidocaine, quinidine, meperidine, pentazocine, chlorpheniramine, and methacyclin were compared in animal species and humans. In these two parameters, a statistically significant correlation between animals and humans was obtained, when the parameters were plotted on a log-log scale. The correlation coefficient between V_T/fu_T was significantly higher than that between the apparent volumes of distribution (p V_T/fu_T of various basic drugs in animals and that in humans. Prediction of the apparent volume of distribution in humans using animal data of V_T/fu_T,plasma unbound fraction, blood volume, and blood-to-plasma concentration ratio in humans was successful for most of drugs studied.