TRANSFER OF CLONIDINE AND DEXMEDETOMIDINE ACROSS THE ISOLATED-PERFUSED HUMAN PLACENTA

Background: The placental transfer of the alpha(2) receptor agonist cl onidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more alpha(2)-selectiv e agonist dexmedetomidine. Methods: Term placentas were obtained immed iately after delivery with maternal consent and a 2-hour recycling per fusion of a single placental cotyledon was performed. Disappearance fr om the maternal circulation, accumulation in placental tissue and appe arance in the fetal circulation of clonidine or dexmedetomidine with t he reference compound antipyrine were followed in 4 experiments for bo th drugs. Results: 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 dex medetomidine 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 t he 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 transf er indexes, describing maternal-to-fetal transfer of dexmedetomidine a nd clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively (P<0.05). Conclusions: Dexmedet omidine disappeared faster than clonidine from the maternal circulatio n, while even less dexmedetomidine was transported into the fetal circ ulation. This was due to its greater placental tissue retention, the b asis for which probably is the higher lipophilicity of dexmedetomidine . (C) Acta Anaesthesiologica Sandinavica 41 (1997).