Abstract：
:The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five subjects each. Serum aldosterone levels, ACE activity, and sitting blood pressure were determined, as were pharmacokinetic parameters of fosinoprilat, the active diacid of fosinopril. In a dose-tolerance study (study II), 80 and 160 mg of the drug were administered in doses of 40 mg bid and 80 mg bid for 2 weeks. Pharmacokinetics were determined on days 1 and 14, and blood pressure and ACE activity were measured daily. One hour after all doses of fosinopril, serum ACE activity was undetectable. Peak blood levels of fosinoprilat occurred at about 3 hours after dosing, and linear kinetics of the diacid were observed. ACE activity remained undetectable for more than 24 hours after the treatment was stopped in study II. Serum aldosterone levels were decreased by 50% of baseline values in both studies. In study I, maximal reductions in mean blood pressure occurred approximately 6 hours postdose; once-daily doses of 20 mg or greater achieved reductions of 11.3 to 21.6% (P less than or equal to .05, compared with placebo reductions). Fosinopril was well tolerated. Subjects reported only mild gastrointestinal complications at doses of 80 mg/day or higher. These data show that fosinopril is a safe and effective inhibitor of ACE with a long duration of action on serum ACE activity.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Duchin KL,Waclawski AP,Tu JI,Manning J,Frantz M,Willard DAdoi
10.1002/j.1552-4604.1991.tb01887.xsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
58-64issue
1eissn
0091-2700issn
1552-4604journal_volume
31pub_type
临床试验,杂志文章abstract：:We administered 0.5-and 1.0-mg doses of bumetanide intravenously to eight normal subjects with and without pretreatment with probenecid. Probenecid did not effect either the cumulative response or the time course of response of bumetanide. These results are in contrast to results reported in dogs but consistent with s...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb01772.x
更新日期：1981-07-01 00:00:00
abstract：:Two phase I open-label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end-stage renal disease (ESRD) undergoing hemodialysis and subjects with varying degrees of hepatic impairment; both studies included a matched control g...
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pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1992-06-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1993-09-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
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更新日期：1995-04-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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doi：10.1002/j.1552-4604.1990.tb03437.x
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pub_type： 杂志文章,评审
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1987-07-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期：1994-03-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1982.tb02644.x
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pub_type： 杂志文章
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1992.tb03850.x
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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更新日期：1995-08-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1980.tb01718.x
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