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连续非卧床腹膜透析期间喹那普利及其活性代谢物喹那普利拉的药代动力学

Pharmacokinetics of quinapril and its active metabolite quinaprilat during continuous ambulatory peritoneal dialysis.

作者信息

Swartz R D, Starmann B, Horvath A M, Olson S C, Posvar E L

机构信息

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0364.

出版信息

J Clin Pharmacol. 1990 Dec;30(12):1136-41. doi: 10.1002/j.1552-4604.1990.tb01857.x.

DOI:10.1002/j.1552-4604.1990.tb01857.x
PMID:2273086
Abstract

The pharmacokinetics of quinapril, a novel angiotensin converting enzyme (ACE) inhibitor, and its active metabolite, quinaprilat, were determined following a single 20-mg oral dose of quinapril in six patients with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD). Overall, quinapril was well tolerated by these CAPD patients, with mild and transient side effects, not unexpected in this clinical setting, which included pruritus, headache, nausea, and cough. Blood pressure reduction was observed in four of six patients, with onset reliably two to four hours after dosing and duration up to 48 hours, associated with quinaprilat concentrations in plasma above 90 ng/mL for at least 33 hours postdose. Two patients experienced significant hypotension, systolic blood pressure below 90 mm Hg, which responded promptly to oral fluid administration and/or reduction in dialysate tonicity. The pharmacokinetic profile of quinapril in these CAPD patients was not significantly different from that previously observed in healthy subjects with normal renal function and in patients with moderate to severe renal dysfunction not yet requiring dialysis (RDND). The apparent elimination half-life of quinapril was approximately one hour, with negligible dialysate excretion. The pharmacokinetic profile of quinaprilat in these CAPD patients was similar to that previously observed in patients with RDND. The elimination half-life of quinaprilat was markedly prolonged when compared to that in healthy subjects and averaged 20 hours, with only a small amount of quinaprilat excreted in dialysate (mean = 2.6% of total dose).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在6例接受持续性非卧床腹膜透析(CAPD)的慢性肾衰竭患者中,口服单剂量20毫克喹那普利后,测定了新型血管紧张素转换酶(ACE)抑制剂喹那普利及其活性代谢产物喹那普利拉的药代动力学。总体而言,这些CAPD患者对喹那普利耐受性良好,有轻微且短暂的副作用,在这种临床情况下并不意外,包括瘙痒、头痛、恶心和咳嗽。6例患者中有4例血压下降,给药后2至4小时可靠起效,持续时间长达48小时,与给药后至少33小时血浆中喹那普利拉浓度高于90纳克/毫升有关。2例患者出现显著低血压,收缩压低于90毫米汞柱,口服补液和/或降低透析液张力后迅速缓解。这些CAPD患者中喹那普利的药代动力学特征与先前在肾功能正常的健康受试者以及尚未需要透析的中度至重度肾功能不全患者(RDND)中观察到的情况无显著差异。喹那普利的表观消除半衰期约为1小时,透析液排泄可忽略不计。这些CAPD患者中喹那普利拉的药代动力学特征与先前在RDND患者中观察到的情况相似。与健康受试者相比,喹那普利拉的消除半衰期明显延长,平均为20小时,透析液中仅排泄少量喹那普利拉(平均占总剂量的2.6%)。(摘要截短至250字)

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Pharmacokinetics of quinapril and its active metabolite quinaprilat during continuous ambulatory peritoneal dialysis.连续非卧床腹膜透析期间喹那普利及其活性代谢物喹那普利拉的药代动力学
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引用本文的文献

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Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders.喹那普利:其在心血管疾病中的药理学及治疗应用的进一步更新
Drugs. 2002;62(2):339-85. doi: 10.2165/00003495-200262020-00009.
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Clinical pharmacokinetics of vasodilators. Part I.血管扩张剂的临床药代动力学。第一部分。
Clin Pharmacokinet. 1998 Jun;34(6):457-82. doi: 10.2165/00003088-199834060-00003.
3
Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure.血管紧张素转换酶(ACE)抑制剂在肾衰竭患者中的临床药代动力学
Clin Pharmacokinet. 1993 Mar;24(3):230-54. doi: 10.2165/00003088-199324030-00005.
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Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure.终末期肾衰竭患者服用低剂量喹那普利后喹那普利拉的药代动力学和药效学
Eur J Clin Pharmacol. 1993;44 Suppl 1:S53-6. doi: 10.1007/BF01428395.
5
Quinapril hydrochloride effects on renal function in patients with renal dysfunction and hypertension: a drug-withdrawal study.盐酸喹那普利对肾功能不全合并高血压患者肾功能的影响:一项撤药研究。
Cardiovasc Drugs Ther. 1994 Apr;8(2):271-5. doi: 10.1007/BF00877336.
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Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders.喹那普利。对其在心血管疾病中的药理学和治疗效果的重新评估。
Drugs. 1994 Aug;48(2):227-52. doi: 10.2165/00003495-199448020-00008.