Conti I, Tridico R V, Duan L, Caccia S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Res Commun Chem Pathol Pharmacol. 1991 Feb;71(2):163-74.
The kinetics of l-fenfluramine (l-F) are dose-dependent in man and rats, suggesting self-inhibition of metabolism and saturation of microsomal enzymes. Possible alterations in the oxidative metabolism of model drug substrates were therefore evaluated in rats given l-F orally (12.5 mg/kg). The compound slightly impaired the clearance of antipyrine but had no effect on the kinetics of highly extracted compounds such as lidocaine. l-F did not alter the hepatic content of the main components of the cytochrome P-450 system and did not affect the in vitro metabolism of enzyme activity markers, even after daily doses of 12.5 mg/kg. It was concluded that at doses with dose-dependent behaviour l-F may impair clearance of drugs such as antipyrine and that this interaction most probably occurs through inhibition of specific isoenzymes involved in the metabolism of the test substrate.
左旋芬氟拉明（l-F）的动力学在人和大鼠中呈剂量依赖性，提示其代谢存在自我抑制以及微粒体酶的饱和。因此，在口服给予l-F（12.5mg/kg）的大鼠中评估了模型药物底物氧化代谢的可能改变。该化合物轻微损害了安替比林的清除率，但对利多卡因等高摄取化合物的动力学没有影响。即使在每日剂量为12.5mg/kg后，l-F也未改变细胞色素P-450系统主要成分的肝脏含量，且不影响酶活性标志物的体外代谢。得出的结论是，在具有剂量依赖性行为的剂量下，l-F可能损害安替比林等药物的清除率，并且这种相互作用很可能是通过抑制参与受试底物代谢的特定同工酶而发生的。
