The pharmacokinetics of the new angiotensin converting enzyme (ACE) inhibitor benazepril.HCl were evaluated in healthy male volunteers. The single dose kinetics were established from data of 62 subjects receiving an oral 10 mg dose of the drug. The steady state kinetics were investigated in 15 subjects after once-daily oral doses of 5, 10 or 20 mg. The compound is a prodrug which, on absorption, is hydrolysed to the pharmacologically active metabolite benazeprilat. Thus, plasma concentrations and urinary excretion of parent compound and active metabolite were determined. Benazepril.HCl was rapidly absorbed (tmax = 0.5 h) and rapidly eliminated from plasma (t1/2 = 0.6 h). Only trace amounts were excreted unchanged in urine. The drug was rapidly metabolized to benazeprilat (tmax = 1.5 h). The elimination of the metabolite from plasma was biphasic. About 80 per cent of benazeprilat formed was eliminated within 24 h (t 1/2 = 2.7 h), whereas the terminal phase (t1/2 = 22.3 h) controlled a minor amount of elimination. About 17 per cent of dose was excreted in the 24-h urine as benazeprilat. The drug disposition did not change during repeated oral dosing and only small accumulation of the metabolite occurred. The accumulation ratio was 1.20 for AUC and 1.24 for urinary excretion. The effective half-life for accumulation was estimated at about 10-11 h. The comparison with other ACE inhibitors showed similarities but also marked differences with respect to the drug kinetics and excretion.

Adult↗

PubMedDate not supplied

Delayed biliary drainage is common in asymptomatic post-cholecystectomy volunteers.

A commonly used diagnostic criterion for sphincter of Oddi dysfunction is delayed drainage of contrast media from the bile ducts at endoscopic retrograde cholangiography (ERC), which is defined as the persistence of contrast greater than 45 min after injection. We performed ERC in 11 asymptomatic post-cholecystectomy volunteers for the purpose of evaluating biliary drainage time. In an attempt to more accurately quantify emptying, concomitant scintigraphy was performed at the time of ERC and contrast drainage. Sufficient contrast mixed with technetium-99m sulfur colloid to completely fill out the intra-hepatic tree was injected (mean volume, 9 ml) and the volunteers remained in the prone position during imaging. The length of time from cholecystectomy, bile duct size, volume of contrast injected, and scintigraphic T1/2s did not correlate with drainage time at ERC. At 45 min after injection the degree of residual contrast filling was scored as: empty in three volunteers, almost empty in one, one-fourth full in 5, and one-half full in two. Therefore, 7 of the 11 asymptomatic volunteers (63%) had delayed drainage. Even if more stringent criteria for delayed drainage were used (ducts one-half filled), 2 of the 11 (18%) had abnormal drainage. The frequent occurrence of delayed drainage in these asymptomatic post-cholecystectomy volunteers challenges the validity of the 45-min delayed drainage criterion for sphincter of Oddi dysfunction.

Adult↗