PT  - JOURNAL ARTICLE
AU  - G Veereman-Wauters
AU  - J Monbaliu
AU  - W Meuldermans
AU  - R Woestenborghs
AU  - M Verlinden
AU  - J Heykants
AU  - C D Rudolph
TI  - Study of the placental transfer of cisapride in sheep. Plasma levels in the pregnant ewe, the fetus, and the lamb.
DP  - 1991 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 168--172
VI  - 19
IP  - 1
4099  - http://dmd.aspetjournals.org/content/19/1/168.short
4100  - http://dmd.aspetjournals.org/content/19/1/168.full
SO  - Drug Metab Dispos1991 Jan 01; 19
AB  - 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.