Steady-state pharmacokinetics and pharmacodynamics of benazeprilat in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.
The effects of the simultaneous steady-state intravenous infusion of benazeprilat, the active metabolite of benazepril HCl, and angiotensin I (AI) on mean arterial blood pressure were investigated in the conscious, unrestrained spontaneously hypertensive rat (SHR) and its normotensive parent strain, the Wistar-Kyoto (WKY) rat. A competitive inhibition model is applied and the limits of its validity are discussed. Deviations from the model are apparent at high drug infusion rates and may relate to the effect of benazeprilat on the clearance of AI. The strains differ in the amounts of angiotensin converting enzyme (ACE) or responsiveness to angiotensin II (AII), the drug clearances, and either the pharmacology or the distribution of the drug. Since the latter two differences are drug dependent, prediction between strains is rendered difficult. This steady-state approach relates the hypertension in the SHR to the amount of ACE or responsiveness to AII and renal function.
LeRoy
S
S
Basic Pharmaceutics Research, CIBA-GEIGY Corporation, Ardsley, New York 10502.
Berner
B
B
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000803:Angiotensin I; C052133:benazeprilat