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- W2044607430 abstract "The disposition characteristics of pentopril (the ethyl ester) and its active carboxylic acid metabolite (CGS 13934) were determined in conscious rats after separate intravenous administrations of both compounds. The relationship between plasma concentration and pharmacological effect was also evaluated. The extent of apparent bioavailability of the active metabolite was determined after oral administration of pentopril. Pharmacokinetic parameters were calculated from the plasma concentration-time data for both the parent drug and its active metabolite after their separate intravenous administrations using a one-compartment model for the drug and a two-compartment model for the metabolite. The elimination half-life for the drug was approximately 1 min. The elimination half-life for the metabolite was 13 min (SD, +/- 3.5, n = 4) after its direct intravenous administration, but increased to an apparent half-life of 20 min (SD +/- 5, n = 5) when formed in vivo as a metabolite. Comparison of the formation rate of the metabolite and the elimination rate of the parent drug indicated that the parent drug was rapidly and completely hydrolyzed to the acid metabolite as soon as it reached the systemic circulation. No parent drug was detected in plasma after its oral administration. The apparent bioavailability of the acid metabolite was 66% after oral drug administration. A close relation between inhibition of pressor response to angiotensin I (AI) and plasma concentration of the active metabolite was observed when plotted against time after drug or metabolite administration. A Michaelis-Menten function correlated (multiple r2:0.995) well between effect and plasma metabolite concentration with mean concentration for 50% of maximum inhibition, IC50, of 3.6 X 10(-7) M (0.11 microgram/mL)." @default.
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- W2044607430 date "1985-09-01" @default.
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- W2044607430 title "Disposition of Pentopril, a New Orally Active Angiotensin-Converting Enzyme Inhibitor, and Its Active Metabolite in Rats" @default.
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- W2044607430 doi "https://doi.org/10.1002/jps.2600740908" @default.
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