Document Detail


The clinical pharmacokinetics of quinapril.
MedLine Citation:
PMID:  2705643     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose proportional following single oral 2.5- to 80-mg Q doses. Q absorption and hydrolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL following 40-mg Q). Dose-proportional QT area under the curve and dose-independent percent of dose excreted in urine as QT demonstrate that the extent of Q conversion to QT is constant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clearances of 1,850 and 220 mL/min, respectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactivity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketopiperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an administered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary excretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clearance of both Q and QT is independent of dose, and metabolism to compounds other than QT is not extensive.
Authors:
S C Olson; A M Horvath; B M Michniewicz; A J Sedman; W A Colburn; P G Welling
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Angiology     Volume:  40     ISSN:  0003-3197     ISO Abbreviation:  Angiology     Publication Date:  1989 Apr 
Date Detail:
Created Date:  1989-05-18     Completed Date:  1989-05-18     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0203706     Medline TA:  Angiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  351-9     Citation Subset:  IM    
Affiliation:
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan.
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MeSH Terms
Descriptor/Qualifier:
Absorption
Adult
Angiotensin-Converting Enzyme Inhibitors / blood,  pharmacokinetics*,  urine
Half-Life
Humans
Isoquinolines / blood,  pharmacokinetics*,  urine
Male
Random Allocation
Tetrahydroisoquinolines*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Isoquinolines; 0/Tetrahydroisoquinolines; 82586-55-8/quinapril; 82768-85-2/quinaprilat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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