Veereman-Wauters G, Monbaliu J, Meuldermans W, Woestenborghs R, Verlinden M, Heykants J, Rudolph C D
Department of Pediatrics, University of California Medical Center, San Francisco.
Drug Metab Dispos. 1991 Jan-Feb;19(1):168-72.
The placental transfer of cisapride, a new prokinetic agent, was studied in a sheep model. The pharmacokinetics of cisapride were studied in the lamb, the pregnant ewe, and the fetus by obtaining blood samples from chronically implanted arterial catheters. Comparable pharmacokinetic parameters were found in the lamb and the adult sheep: half-life, 1.39-1.83 hr; total plasma clearance, 1998-2160 ml/kg/hr; AUC, 92.6-100.1 ng.hr/ml. Cisapride plasma concentrations after continuous infusion were predicted correctly based on the parameters obtained after iv bolus. There was a materno-fetal transfer of cisapride following a single iv bolus administered to the mother. Cisapride crossed the placenta within 5 min and equilibrated with maternal plasma within 20 to 30 min after dosing. The average fetal-to-maternal plasma concentration ratio was 0.71. The amniotic fluid also contained measurable amounts of cisapride. The protein binding of cisapride in maternal and fetal plasma is 89.0% and 88.4%, respectively; the free fraction is 4 times larger than in humans. Cisapride crosses the ovine placental barrier. The sheep placenta is less permeable than the human placenta, but the higher free fraction of cisapride facilitates placental transfer.
在绵羊模型中研究了新型促动力药西沙必利的胎盘转运情况。通过从长期植入的动脉导管采集血样，研究了西沙必利在羔羊、怀孕母羊和胎儿体内的药代动力学。在羔羊和成年绵羊中发现了可比的药代动力学参数：半衰期为1.39 - 1.83小时；总血浆清除率为1998 - 2160毫升/千克/小时；AUC为92.6 - 100.1纳克·小时/毫升。基于静脉推注后获得的参数，能够正确预测持续输注后西沙必利的血浆浓度。给母亲单次静脉推注后，西沙必利存在母胎转运。给药后5分钟内西沙必利穿过胎盘，并在20至30分钟内与母体血浆达到平衡。胎儿与母体血浆浓度的平均比值为0.71。羊水也含有可测量量的西沙必利。西沙必利在母体和胎儿血浆中的蛋白结合率分别为89.0%和88.4%；游离部分比人类大4倍。西沙必利穿过绵羊胎盘屏障。绵羊胎盘的通透性低于人类胎盘，但西沙必利较高的游离部分促进了胎盘转运。
