Modulation by dietary salt of verapamil disposition in humans
Modulation by dietary salt of verapamil disposition in humans
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DOI：
10.1161/01.cir.98.24.2702
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发表时间：
1998-12-15
期刊：
影响因子：
37.8
通讯作者：
Roden, DM
中科院分区：
文献类型：
--
作者：
Darbar, D;Fromm, MF;Roden, DM
背景-肠道是日益被广泛认可的药物首过代谢部位。在这项研究中，我们确定了膳食盐对维拉帕米稳态处置的影响，维拉帕米是一种经历广泛首过代谢的药物。方法和结果-8 名正常志愿者每天口服两次 120 毫克外消旋维拉帕米，持续 21 天。在第 7、14 和 21 天静脉注射氘化维拉帕米与早晨口服剂量共同给药后，测定了维拉帕米对映体的处置动力学。每个研究日之前都有 7 天的固定盐饮食：在 5 名受试者中，最初的研究是在低盐（10 mEq/d）饮食期间进行的，第二项研究是在高盐（400 mEq/d）饮食期间进行的，第三名受试者采用低盐饮食，而其他三名受试者的饮食顺序相反。两种未标记的对映体（即口服治疗）的血浆浓度显着（P
Background-The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism.Methods and Results-Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d)diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed. Plasma concentrations of both unlabeled enantiomers (ie, from oral therapy) were significantly (P