PREDICTION OF THE VOLUMES OF DISTRIBUTION OF BASIC DRUGS IN HUMANS BASED ON DATA FROM ANIMALS

The appearent volume of distribution-after distribution equilibrium and the ratio of distributive tissue volume to the unbound fraction in the tissue (VT/fuT) of 10 weak basic drugs, i.e., chlorpromazine, imipramine, propranolol, disopyramide, lidocaine, quinidine, meperidine, pentazocine chlorpheniramine and methacyclin, were compared in animal species [rat, dog, monkey, mouse, rabbit and sheep] and humans. In these 2 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 VT/fuT was significantly higher than that between the apparent volumes of distribution (P < 0.05). There was little difference between VT/fuT of various basic in animals and that in humans. Prediction of the apparent volume of distribution in humans using animal data of VT/fuT, plasma unbound fraction, blood volume and blood-to-plasma concentration ration in humans was successful for most of drugs studied.