Dale O, Gandolfi A J, Brendel K, Schuman S
Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724.
Br J Anaesth. 1988 May;60(6):692-6. doi: 10.1093/bja/60.6.692.
The influence of the volatile anaesthetic agents enflurane, isoflurane, halothane and the halothane metabolite trifluoroacetic acid was studied on the hepatic elimination of diazepam, by incubating precision-cut slices of rat liver in a closed system. The impact of anaesthetic-induced action on enzyme activity and diazepam binding to human serum albumin (HSA) was assessed in protein free and protein containing buffers, respectively. Human serum albumin reduced the elimination of diazepam by 12 and 50% at concentrations of 1 and 10 mg ml-1, respectively. In the absence of albumin, halothane 1 mmol litre-1 reduced the elimination of diazepam by 13%, whereas enflurane at 1.5 mmol litre-1 caused a reduction of 8%. No effect was seen from isoflurane 1 mmol litre-1 and trifluoroacetic acid 4 mmol litre-1. In the presence of the highest concentration of albumin, however, an increased elimination of diazepam of 24% resulted from exposure to enflurane and trifluoroacetic acid, while no statistically significant changes were seen for isoflurane and halothane. The present work supports the view that volatile anaesthetic agents may cause pharmacokinetic drug interactions by interference with both enzyme activity and drug protein binding.
通过在封闭系统中孵育大鼠肝脏的精密切片，研究了挥发性麻醉剂恩氟烷、异氟烷、氟烷以及氟烷代谢产物三氟乙酸对肝脏消除地西泮的影响。分别在无蛋白和含蛋白缓冲液中评估了麻醉诱导作用对酶活性以及地西泮与人血清白蛋白（HSA）结合的影响。人血清白蛋白在浓度为1和10 mg/ml时，分别使地西泮的消除率降低了12%和50%。在无白蛋白的情况下，1 mmol/L的氟烷使地西泮的消除率降低了13%，而1.5 mmol/L的恩氟烷使消除率降低了8%。1 mmol/L的异氟烷和4 mmol/L的三氟乙酸未见影响。然而，在白蛋白最高浓度存在时，暴露于恩氟烷和三氟乙酸导致地西泮的消除率增加了24%，而异氟烷和氟烷未见统计学上的显著变化。目前的研究支持这样一种观点，即挥发性麻醉剂可能通过干扰酶活性和药物蛋白结合而导致药代动力学药物相互作用。
