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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1980-8-25
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pubmed:abstractText |
The pharmacokinetics of hydralazine (H) and its acid-labile hydrazone metabolites were compared in rapid and slow acetylators. Following a 20-mg intravenous infusion, the elimination half-life (t 1/2 beta) and the apparent volume of distribution of H did not differ between the two groups. Plasma clearance estimates approached hepatic blood flow. When a single 100-mg dose of H was given orally, the area under the plasma concentration-time curve (AUC) and a systemic availability (theta) in slow acetylators were, on the average, twice as high as in the rapid acetylators, indicating a difference in the extent of first-pass metabolism of the drug. Furthermore, the observed theta in the slow individuals exceeded theoretical predictions. Hence saturation of first-pass metabolism of H is suggested, and a nonlinear relationship between AUC and oral dose of H was indeed observed in the three subjects studied with two doses. The half-life of decline of the acid-labile metabolites was similar to the t 1/2 beta of H. The AUCs for metabolies were 4--12 times larger than for the parent drug. However, the ratio between the metabolite AUC and drug AUC did not differ irrespective of routes of administration or the acetylator status.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0090-466X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53-68
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7381691-Acetylation,
pubmed-meshheading:7381691-Administration, Oral,
pubmed-meshheading:7381691-Adult,
pubmed-meshheading:7381691-Chemical Phenomena,
pubmed-meshheading:7381691-Chemistry,
pubmed-meshheading:7381691-Female,
pubmed-meshheading:7381691-Humans,
pubmed-meshheading:7381691-Hydralazine,
pubmed-meshheading:7381691-Hydrazones,
pubmed-meshheading:7381691-Injections, Intravenous,
pubmed-meshheading:7381691-Kinetics,
pubmed-meshheading:7381691-Male,
pubmed-meshheading:7381691-Phenotype,
pubmed-meshheading:7381691-Time Factors
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pubmed:year |
1980
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pubmed:articleTitle |
Pharmacokinetics of hydralazine and its acid-labile hydrazone metabolites in relation to acetylator phenotype.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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