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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The disposition of [14C]-labelled benazepril HCl in normal adult volunteers after single and repeated oral dose.

1. The disposition of [14C]-labelled benazepril HCl, an ACE-inhibitor, was studied in four normal adult volunteers after a single oral dose of 20 mg and after repeated doses of 20 mg once daily for 5 days. Radioactivity was measured in plasma, urine and faeces. The prodrug ester benazepril and the pharmacologically active metabolite benazeprilat were determined quantitatively in plasma and urine by a g.c.-m.s. method. The pattern of metabolites in urine was analysed semiquantitatively by h.p.l.c.-radiometry. 2. After a single oral dose at least 37% was absorbed, as indicated by urinary recovery. The peak plasma concentration of benazepril (0.58 +/- 0.13 nmol/g (SD] was observed at 0.5h after dose, indicating rapid absorption. Peak concentrations of radioactivity (1.88 +/- 0.48 nmol/g) and of active benazeprilat (0.84 +/- 0.25 nmol/g) were observed at 1 h after dose, demonstrating rapid bioactivation. 3. The area under the plasma curve (AUC0-96 h) of total radioactivity amounted to 9.7 +/- 1.1 (nmol/g)h, 5% of which was accounted for by benazepril and about 50% by benazeprilat. 4. Over 9 days 96.8 +/- 0.5% of the dose was excreted in urine and faeces. Urinary excretion accounted for 37.0 +/- 6.0% of the dose, 80% of which was recovered in the first 8 h after dosing. 5. In urine, only 0.4% of the dose (1% of the radioactivity) was excreted as unchanged benazepril, indicating that the compound was extensively metabolized. Benazeprilat accounted for 17% of the dose (about half of the radioactivity; 0-96 h). Glucuronide conjugates of benazepril and benazeprilat constituting approximately 11% and 22% of the radioactivity (about 4% and 8% of the dose; 0-48 h) were tentatively identified. 6. Repeated oral treatment with benazepril HCl did not influence the pharmacologically relevant kinetics and disposition parameters.[1]


  1. The disposition of [14C]-labelled benazepril HCl in normal adult volunteers after single and repeated oral dose. Waldmeier, F., Kaiser, G., Ackermann, R., Faigle, J.W., Wagner, J., Barner, A., Lasseter, K.C. Xenobiotica (1991) [Pubmed]
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