Plasma angiotensin converting enzyme activity and pharmacokinetics of benazepril and benazeprilat in cats after single and repeated oral administration of benazepril.HCl

The plasma pharmacokinetics of benazepril and its active metabolite, benaze prilat, were determined in cats after oral administration of benazepril.HCl at dosages of 0.25, 0.5 and 1.0 mg/kg as a single dose (n = 5 per group) a nd after once daily application for 8 days (n = 6 per group). Pharmacodynam ics were assessed by measurement of plasma angiotensin converting enzyme (A CE) activity. After single administration of benazepril.HCl, maximum benazepril concentra tions were recorded at the first sample (2 h) and declined relatively rapid ly with an elimination half life (t(1/2)) of 1.4 h. Highest benazeprilat co ncentrations were recorded at the first sample (2 h) in most cats and decli ned biphasically with half lives of each phase of 2.4 and 27.7 h. With repe ated administration, plasma benazeprilat concentrations accumulated slightl y with accumulation ratios (R) of 1.46, 1.36 and 1.24 for the 0.25, 0.5 and 1.0 mg/kg dosages of benazepril. HCl, respectively (median value of 1.36 f or all dosages). All three dosages of benazepril.HCl caused marked inhibition of plasma ACE activity in all cats, The maximum effect (E-max, % inhibition of ACE as com pared to baseline) was greater than or equal to 98% after single and 100% w ith repeated administration. The duration of action of benazepril.HCl was l ong, with > 87% (single) and > 90% (repeat) inhibition of plasma ACE persis ting 24 h after dosing. Benazepril.HCl was well tolerated in all animals. Dosages of 0.25-1.0 mg/kg benazepril.HCl once daily are recommended for clinical testing in cats.