Ex Vivo Human Placental Transfer of Rifampin and Rifabutin

OBJECTIVE The purpose of this study was to determine the ex vivo human placental transfer of rifampin and rifabutin. METHODS Seven placentas from uncomplicated term vaginal or cesarean deliveries were studied utilizing the ex vivo single cotyledon perfusion system. Antipyrine was used for the reference compound in the determination of the clearance indices of rifampin and rifabutin. RESULTS The clearance indices of rifampin at maternal concentrations of 1.0 and 10.0 mug/ml were 0.12 +/- 0.05 and 0.12 +/- 0.11, respectively. The clearance indices of rifabutin at maternal concentrations of 1.0 and 10.0 mug/ml were 0.44 +/- 0.11 and 0.37 +/- 0.15, respectively. CONCLUSIONS Because of its greater lipophilicity, rifabutin was found to have a greater clearance than rifampin. However, because of rifabutin's trend toward greater deposition in tissue, there was proportionately less accumulation of rifabutin in the fetal circulation when compared to rifampin.