Cristofol C, Carretero A, Fernandez M, Navarro M, Sautet J, Ruberte J, Arboix M
Unitat de Farmacologia, UAB, Bellaterra, Spain.
Eur J Drug Metab Pharmacokinet. 1995 Jul-Sep;20(3):167-71. doi: 10.1007/BF03189665.
Neither netobimin (NTB) nor its metabolite albendazole (ABZ) were found in plasma after an oral administration of 20 mg/kg of NTB to pregnant ewes during the last third of gestation. ABZ metabolites, albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) were found in plasma 30 min and 2 h, respectively, after administration. The maximal plasma concentration (Cmax) of ABZSO was detected at 11.6 +/- 1.0 h and for ABZSO2 at 16.5 +/- 2.3 h. The plasma levels of the latter remained constant for 36 h, and decreased as ABZSO was removed from the blood. Jugular plasma levels of both metabolites did not differ significantly from those observed in the ovarian vein, suggesting that there were no exchanges between foetal and placental tissues. Both metabolite concentrations were similar in the umbilical vein and artery and in the amniotic and allantoic fluids, their values were half the maternal plasma concentration, leading to the conclusion that there was transplacental movement of metabolites. Both metabolites reached the foetus and could be responsible for the teratogenicity of NTB in sheep.
在妊娠后期给怀孕母羊口服20mg/kg的奈托比明（NTB）后，血浆中未检测到奈托比明（NTB）及其代谢产物阿苯达唑（ABZ）。给药后30分钟和2小时，血浆中分别检测到阿苯达唑代谢产物阿苯达唑亚砜（ABZSO）和阿苯达唑砜（ABZSO2）。阿苯达唑亚砜（ABZSO）的最大血浆浓度（Cmax）在11.6±1.0小时检测到，阿苯达唑砜（ABZSO2）在16.5±2.3小时检测到。后者的血浆水平在36小时内保持恒定，并随着阿苯达唑亚砜（ABZSO）从血液中清除而下降。两种代谢产物的颈静脉血浆水平与卵巢静脉中观察到的水平无显著差异，表明胎儿和胎盘组织之间没有交换。脐静脉和动脉以及羊水和尿囊液中的两种代谢产物浓度相似，其值为母体血浆浓度的一半，得出代谢产物存在经胎盘转运的结论。两种代谢产物均到达胎儿体内，可能是导致NTB对绵羊致畸的原因。
