EFFECTS OF CALCIUM-CHANNEL BLOCKERS ON THE PHARMACOKINETICS OF PROPRANOLOL STEREOISOMERS

被引：24

作者：

HUNT, BA ^{[1
]}

BOTTORFF, MB ^{[1
]}

HERRING, VL ^{[1
]}

SELF, TH ^{[1
]}

LALONDE, RL ^{[1
]}

机构：

[1] UNIV TENNESSEE,CTR HLTH SCI,DEPT CLIN PHARM,26 S DUNLAP ST,SUITE 202,MEMPHIS,TN 38163

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 1990年 / 47卷 / 05期

关键词：

D O I：

10.1038/clpt.1990.79

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 < 0.05 versus control). With verapamil, d‐propranolol oral clearance decreased 32% (p < 0.05), and 1‐propranolol oral clearance decreased 26% (p < 0.05). The unbound fraction of d‐propranolol was higher than that of 1‐propranolol (p < 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 < 0.05). Verapamil caused a stereoselective effect and increased the d/1 ratio of propranolol serum concentrations (p < 0.05) and decreased the d/1 ratio of oral clearance (p < 0.05). Clinical Pharmacology and Therapeutics (1990) 47, 584–591; doi: © 1990 American Society for Clinical Pharmacology and Therapeutics

引用

页码：584 / 591

页数：8

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