Augustijns P, Jongsma H W, Verbeke N
Laboratory of Clinical Pharmacy, University of Leuven, Belgium.
Dev Pharmacol Ther. 1991;17(3-4):191-9. doi: 10.1159/000457522.
Chloroquine is frequently used during pregnancy in malaria-endemic countries, but no data are available about fetal exposure to the drug. Prophylactic use during labour to obtain effective concentrations in the newborn is also documented. In the present study, the placental transfer of chloroquine was investigated in the pregnant, near-term sheep model. Chronic catheterization allowed blood sampling of maternal and fetal blood. Following a single intramuscular injection or intravenous infusion to the ewe, chloroquine was slowly distributed to the fetus. Peak concentrations in the fetus reached up to +/- 280 ng/ml within 2-4 h after administration while maximal concentrations in the mother reached up to 2,850 ng/ml. The terminal half-life of chloroquine in pregnant sheep was very long, amounting to 65.1 +/- 34.9 h (range 27.4-119 h). Tissue binding was high, as reflected by the extensive volume of distribution (V(area): 19.0 +/- 11.0 l/kg). Total clearance was equal to 3.42 +/- 0.60 ml/min/kg. The transfer rate of chloroquine from the mother to the fetus was low in all animals. So, the placenta is quite an effective barrier for the drug.
在疟疾流行国家,孕期经常使用氯喹,但尚无关于胎儿接触该药物的数据。也有文献记载在分娩期间预防性使用氯喹以在新生儿体内获得有效浓度。在本研究中,在妊娠晚期绵羊模型中研究了氯喹的胎盘转运情况。通过慢性插管可采集母羊和胎儿的血液样本。给母羊单次肌内注射或静脉输注氯喹后,该药缓慢分布至胎儿体内。给药后2 - 4小时内,胎儿体内的峰值浓度高达±280 ng/ml,而母体中的最大浓度高达2850 ng/ml。氯喹在妊娠绵羊体内的终末半衰期很长,达65.1±34.9小时(范围为27.4 - 119小时)。组织结合率很高,这从其广泛的分布容积(V(area):19.0±11.0 l/kg)可以看出。总清除率为3.42±0.60 ml/min/kg。在所有动物中,氯喹从母体向胎儿的转运率都很低。因此,胎盘对该药物是一个相当有效的屏障。