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Low clearance of cimetidine across the human placenta

MS Ching, GW Mihaly, DJ Morgan, NM Date, KJ Hardy and RA Smallwood

The transfer of cimetidine across the isolated perfused human placenta was examined. Placentas obtained at cesarean section were perfused for 2 hr from both maternal and fetal sides in constant flow recycling systems. Cimetidine was administered as a bolus dose to either the maternal circuit alone (n = 4) or to both maternal and fetal circuits simultaneously (n = 3), to achieve initial concentrations of 4 micrograms/ml. Antipyrine (20 micrograms/ml) and l-leucine (0.25 mM) were administered in like fashion as reference compounds. Two hours after maternal dosage there was equilibration of antipyrine across the placenta, but equilibration of cimetidine was incomplete (fetal/maternal ratio = 0.46 +/- 0.07). The fetal/maternal ratio of l- leucine was greater than unity; consistent with active maternal to fetal transport. Maternal to fetal cimetidine transplacental clearance (0.50 +/- 0.05 ml/min) was 23% of antipyrine clearance. After simultaneous dosage to both maternal and fetal circuits, the l-leucine fetal/maternal ratio was 1.37 +/- 0.08 at 2 hr and maternal and fetal levels of cimetidine and antipyrine were at equilibrium for the duration of the experiment (fetal/maternal ratio of cimetidine = 1.01 +/- 0.02). This study shows that cimetidine is transferred across the human placenta by passive diffusion. In contrast to the rapid placental transfer demonstrated by the majority of drugs studied previously, the placental transfer of cimetidine is slow. We conclude that the human placenta may therefore provide significant protection of the fetus from a single maternally administered dose of cimetidine.

Volume 241, Issue 3, pp. 1006-1009, 06/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1987 by the American Society for Pharmacology and Experimental Therapeutics.