FIG 4.
Effect of maternal pH on elimination of lamivudine from the fetal circulation. In the closed-circuit perfusion setup, both the fetal and maternal sides of the placenta were simultaneously infused with 12 nM [3H]lamivudine. The fetal pH was set to 7.4, whereas the pH in the maternal reservoir was set to 6.5, 7.4, or 8.5. The fetal perfusate was recirculated for 60 min, and then fetal and maternal concentrations of lamivudine were compared. (A) Lamivudine fetal concentration over a 60-min perfusion at pH 6.5 and 8.5 applied on the maternal site. (B) Final ratio between fetal and maternal concentrations at equilibrium showing statistically significant difference between ratios calculated for perfusions at pH 6.5 and pH 8.5 (*, P < 0.05, Kruskal-Wallis test), suggesting involvement of a proton-cation antiporter system in lamivudine transplacental transport. Data are presented as means ± SD (n ≥ 3).