1. The pharmacokinetics of the angiotensin-converting-enzyme (ACE) inhibitor benazepril were evaluated in eight healthy Beagle dogs. Benazepril was administered orally at a dosage of 7.5 mg (about 0.5 mg/kg) both as a single dose and then once daily for 14 consecutive days. The prodrug, benazepril, and its active metabolite, benazeprilat, were measured in plasma using a gas chromatography mass-spectrometry method with mass-selective detection. 2. Benazepril appeared quickly in the plasma (tmax 0.5 h) and was rapidly eliminated by metabolism to benazeprilat. Peak benazeprilat concentrations were attained later (tmax 1.25 h) and declined biphasically with a rapid elimination phase (t1/2 lambda 1 1.1 and 1.7 h after single and the last repeated dose respectively) followed by a terminal elimination phase (t1/2 lambda z 11.7 and 19.0 h after single and repeated dose respectively). The mean residence time for benazeprilat was 15.2 h after the single dose and 17.4 h after the 14th dose. 3. Repeated administration of benazepril produced moderate bioaccumulation of benazeprilat; the ratio of AUC[0-->24 h]'s after the 14th dose as compared with the single dose was 1.47, equivalent to a half-life for accumulation (t1/2acc) of 14.6 h. Steady-state benazeprilat concentrations at peak (Cmax) and trough (Cmin) were reached within three doses. 4. The pharmacodynamics of benazepril were assessed by measurement of plasma ACE activity. After both single doses and at steady-state, benazepril produced inhibition of ACE activity in all dogs that was maximal at peak effect (Emax = 100%) and long-lasting (> 85% inhibition was present at 24 h). The long duration of action of benazepril on plasma ACE is due to the presence of the terminal elimination phase of benazeprilat, even though most of the metabolite is rapidly eliminated from the plasma.
Rat testes have been examined with a panel of lectins that bind specifically to oligosaccharide sequences having terminal or subterminal beta-galactosyl residues in O-linked glycans, or in the outer chains of complex N-linked glycans: Arachis hypogaea (peanut, AHA), Erythrina cristagalli (coral tree, ECA), Ricinus communis (castor bean, RCA120) and Abrus precatorius (jequirity bean, APA) agglutinins. Pretreatment of sections with neuraminidase, beta-galactosidase and removal of alkali-labile O-linked sequences by beta-elimination allowed the structure of these glycans to be further explored. In spermatogonia and spermatocytes there was little evidence of glycans terminating in beta-galactosyl residues, although these were present at non-reducing terminals as sialylgalactosides. The acrosome contained two subsets of O-linked glycans terminating in sialylgalactosides, while the nuclear cap showed at least two subsets of N-linked sialylgalactosyl as well as O-linked glycans. Spermatozoa exhibited minor changes in the pattern of glycosylation, although the overall pattern of beta-galactosyl expression was similar. Binding to Sertoli cells showed the presence of some unsubstituted beta-galactosyl terminals on O-linked glycans but few such N-linked residues, while terminal beta-galactosides were scanty in tubular basement membranes.
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