Galtier P, Alvinerie M
Laboratoire de pharmacologie-toxicologie, Inra, Toulouse, France.
Vet Res. 1996;27(4-5):363-72.
Age-related changes in hepatic drug metabolizing activities of Lacaune ewes were determined in foetal, neonatal, growing, pregnant and adult animals. The ontogenic evolution of cytochrome P450 was compared to those of microsomal monooxygenases and some microsomal and cytosolic transferases. The involvement of two purified izoenzymes P4502B and P4503A was determined in the N-demethylation of various substrates and the hydroxylations of progesterone. An experimental fascioliasis, provoked by the oral administration of 150 metacercariae of Fasciola hepatica to sheep, was proposed as a pathological model. Its effect was measured on the pharmacokinetics of various hepatic tracers and veterinary drugs. The mean residence times of antipyrine, pentobarbital, albendazole and mebendazole were increased in infected lambs with consequences on the urinary excretion of 4-hydroxyantipyrine, prolongation of pentobarbital-induced sleeping time, elimination of albendazole sulfone and reduced mebendazole. The characteristic decrease in liver cytochrome P450 could be responsible for most of the pharmacokinetic and pharmacodynamic changes observed in fluke-infected ruminants.
在胎儿期、新生儿期、生长期、孕期和成年期的拉库内母羊中，测定了与年龄相关的肝脏药物代谢活性变化。将细胞色素P450的个体发育演变与微粒体单加氧酶以及一些微粒体和胞质转移酶的演变进行了比较。确定了两种纯化的同工酶P4502B和P4503A在各种底物的N-去甲基化和孕酮羟化反应中的作用。通过给绵羊口服150只肝片吸虫囊蚴引发实验性片形吸虫病，将其作为一种病理模型。测定了其对各种肝脏示踪剂和兽药药代动力学的影响。感染羔羊中安替比林、戊巴比妥、阿苯达唑和甲苯达唑的平均驻留时间增加，这对4-羟基安替比林的尿排泄、戊巴比妥诱导睡眠时间的延长、阿苯达唑砜的消除以及甲苯达唑的减少均有影响。肝脏细胞色素P450的特征性降低可能是吸虫感染反刍动物中观察到的大多数药代动力学和药效学变化的原因。
