钙通道阻滞剂对普萘洛尔立体异构体药代动力学的影响。
Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers.
作者信息
Hunt B A, Bottorff M B, Herring V L, Self T H, Lalonde R L
机构信息
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
出版信息
Clin Pharmacol Ther. 1990 May;47(5):584-91. doi: 10.1038/clpt.1990.79.
Diltiazem and verapamil inhibit oxidative drug metabolism both in vivo and in vitro. We compared their effects on the stereoselective pharmacokinetics and protein binding of propranolol in 12 subjects. After 6 days of coadministration with racemic propranolol, diltiazem caused decreases of 27% and 24% in d-propranolol and 1-propranolol oral clearances, respectively (p less than 0.05 versus control). With verapamil, d-propranolol oral clearance decreased 32% (p less than 0.05), and 1-propranolol oral clearance decreased 26% (p less than 0.05). The unbound fraction of d-propranolol was higher than that of 1-propranolol (p less than 0.05), but the protein binding was not altered by diltiazem or verapamil. Both drugs therefore decreased the unbound oral clearance of each propranolol enantiomer (p less than 0.05). Verapamil caused a stereoselective effect and increased the d/l ratio of propranolol serum concentrations (p less than 0.05) and decreased the d/l ratio of oral clearance (p less than 0.05).
地尔硫䓬和维拉帕米在体内和体外均抑制药物的氧化代谢。我们比较了它们对12名受试者中普萘洛尔立体选择性药代动力学和蛋白结合的影响。与消旋普萘洛尔合用时6天后，地尔硫䓬使d-普萘洛尔和l-普萘洛尔的口服清除率分别降低了27%和24%（与对照组相比，p<0.05）。使用维拉帕米时，d-普萘洛尔口服清除率降低32%（p<0.05），l-普萘洛尔口服清除率降低26%（p<0.05）。d-普萘洛尔的游离分数高于l-普萘洛尔（p<0.05），但地尔硫䓬或维拉帕米未改变其蛋白结合。因此，两种药物均降低了每种普萘洛尔对映体的游离口服清除率（p<0.05）。维拉帕米产生了立体选择性作用，增加了普萘洛尔血清浓度的d/l比值（p<0.05），并降低了口服清除率的d/l比值（p<0.05）。
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