INTERSPECIES SCALING AND PHARMACOKINETIC PARAMETERS OF 3TC IN HUMANS

3TC is a dideoxy-nucleoside analogue that has demonstrated in-vitro ac tivity against human immunodeficiency virus (HIV). 3TC concentrations in humans were predicted before the initiation of clinical trials by i nterspecies scaling of pharmacokinetic parameters observed in animal s pecies. Clearance and volume of distribution were estimated for humans using linear regression on a log-log scale of each parameter versus b ody weight for rats and dogs. The concentration-time profile and the a verage serum concentration at steady state after various dosage regime ns were estimated as a basis for initial dose selection for clinical t rials. The predicted parameters (clearance of 16.3 L/hr and volume of distribution of 40 L for a 70-kg man) were compared with that observed (mean clearance of 24 L/hr and mean volume of distribution of 96 L, m ean weight of 74 kg) in 20 asymptomatic, HIV positive, volunteers afte r single intravenous doses of 3TC. Interspecies scaling was applied pr ospectively as a rationale for dose selection of 3TC in clinical trial s.