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

Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers.

The absorption of benazepril-HCl (BZPH), an orally active angiotensin-converting enzyme (ACE) inhibitor, in various regions of the gastrointestinal (GI) tract was investigated using an intestinal intubation technique. Thirteen subjects completed this single-dose, three-phase sequential crossover study. The drug (20 mg) was administered either as a 4-hr colonic infusion (COLON) or as a small intestinal infusion (SI) in the first two phases and as an oral bolus solution (ORAL) in the third phase, with a 2-week washout between each treatment. Serial plasma and urine samples were collected for up to 4 days after dosing. BZPH and its active metabolite benazeprilat (BZPL) were determined using a gas chromatography/ mass spectrometry method. BZPH was absorbed rapidly into the bloodstream (Tmax = 0.5 hr after ORAL). Absorption was also rapid for SI, with a postinfusion half-life (0.57 hr) nearly identical to that for ORAL (0.59 hr). The absorption rate after COLON was much slower (lower Cmax and longer Tmax) compared to that after SI, and the apparent half-life (1.7 hr) was prolonged. SI delivered 90%, whereas COLON delivered 23%, of the drug into the systematic circulation as compared to ORAL. BZPL was rapidly formed upon drug absorption. The metabolite-to-drug AUC ratios were comparable for SI and ORAL (8.9 vs 9.7), indicating that first-pass metabolism of BZPH was neither saturable nor input rate dependent. The metabolite-to-drug AUC ratio was reduced for COLON (5.0), indicating that the mechanism of absorption of BZPH in the colon may be different than that after SI and ORAL. Urinary recovery data were consistent with plasma data.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers. Chan, K.K., Buch, A., Glazer, R.D., John, V.A., Barr, W.H. Pharm. Res. (1994) [Pubmed]
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