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.