Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta.

Abstract

The placental transfer of the alpha 2 receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more alpha 2-selective agonist dexmedetomidine. Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs. At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P < 0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% (P < 0.05), while 11.3 (SD 3.3)% (P < 0.05) was retained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively (P < 0.05). Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine.