Placental transfer of lopinavir/ritonavir in the ex vivo human cotyledon perfusion model

Objective This study was done to determine the placental transfer of the human immunodeficiency virus protease inhibitor lopinavir with ritonavir. Study design Twenty-five human cotyledons that were obtained after uneventful pregnancies and deliveries were perfused in an open double circuit with lopinavir (1099-10,606 μg/L) and ritonavir (254-1147 μg/L) at various albumin concentrations (2, 10, and 40 g/L). Results The fetal transfer rate of lopinavir, when combined with ritonavir, was 23.6% ± 6.9% at an albumin concentration of 2 g/L. The fetal transfer rate decreased to 20.7% ± 10% at an albumin concentration of 10 g/L and to 3.3% ± 0.5% at an albumin concentration of 40 g/L. Conclusion The placental transfer of lopinavir, a highly protein-bound molecule, was compatible with passive diffusion of the unbound fraction. Even at physiologic maternal albumin concentrations, the amount of drug transferred into the fetal compartment was well above the 50% inhibitory concentration.