Kkh. Chan et al., SITE-DIFFERENTIAL GASTROINTESTINAL ABSORPTION OF BENAZEPRIL HYDROCHLORIDE IN HEALTHY-VOLUNTEERS, Pharmaceutical research, 11(3), 1994, pp. 432-437
The absorption of benazepril-HCl (BZPH), an orally active angiotensin-
converting enzyme (ACE) inhibitor, in various regions of the gastroint
estinal (GI) tract was investigated using an intestinal intubation tec
hnique. Thirteen subjects completed this single-dose, three-phase sequ
ential crossover study. The drug (20 mg) was administered either as a
4-hr colonic infusion (COLON) or as a small intestinal infusion (SI) i
n the first two phases and as an oral bolus solution (ORAL) in the thi
rd phase, with a 2-week washout between each treatment. Serial plasma
and urine samples were collected for up to 4 days after dosing. BZPH a
nd its active metabolite benazeprilat (BZPL) were determined using a g
as chromatography/mass spectrometry method. BZPH was absorbed rapidly
into the bloodstream (T-max = 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 C-max and longer T-max) compared to that after SI, and t
he apparent half-life (1.7 hr) was prolonged. SI delivered 90%, wherea
s COLON delivered 23%, of the drug into the systematic circulation as
compared to ORAL. BZPL was rapidly formed upon drug absorption. The me
tabolite-to-drug AUC ratios were comparable for SI and ORAL (8.9 vs 9.
7), indicating that first-pass metabolism of BZPH was neither saturabl
e nor input rate dependent. The metabolite-to-drug AUC ratio was reduc
ed for COLON (5.0), indicating that the mechanism of absorption of BZP
H in the colon may be different than that after SI and ORAL. Urinary r
ecovery data were consistent with plasma data. It can be concluded tha
t COLON delivered a smaller amount of drug at a slower absorption rate
to the body than either SI or ORAL.