The tissue distribution, transfer into fetus and milk of nucleoside analogue, lamivudine, were investigated after a single oral administration of ³H-lamivudine to rats at a dose of 2 mg/kg. Plasma protein binding and distribution to erythrocytes of lamivudine were also examined.
1. The radioactivity in most of tissues reached maxima at the first sampling time of 1 hour after oral administration to male rats and the concentrations in ileum, kidney and jejunum were higher than those in other tissues. The levels of radioactivity in most of tissues were below detection limit at 24 hours post dose.
2. The levels of radioactivity in the fetal whole body and tissues were less than 14% of that in the maternal plasma at 1 hour after oral administration to pregnant rats, and were below detection limit up to 48 hours post dose.
3. The radioactivity in milk after oral administration to lactating rats was 5-15 times higher than that in plasma from 4 to 24 hours post dose but it was eliminated rapidly in parallel with those in plasma.
4. The ratio of plasma protein binding and distribution to erythrocytes of ³H-lamivudine in rats, dogs and human was below 7% and 35-48%, at the range of 0.01-10 μg/l in vitro.
5. The ratio of plasma protein binding and distribution to erythrocytes of radioactivity was below 11% and 45-52%, after oral administration of ³H-lamivudine to male rats.