Effect of Hepatic and Renal Failure on the Pharmacokinetics of ACE Inhibitors in Rats.

Abstract

Inhibitors of angiotensin convering enzyme (ACE) are widely used for the treatment of hypertension and cardiac insufficiency. However, such patients demonstrate a wide range diseases and conditions, and hence appropriate ACE inhibitors must be selected depending upon the condition of each individual patient. In the present study, we prepared model rats for various circulatory disorders and investigated which medicine should be used for various disorders based on pharmacokinetic investigations of the ACE inhibitor drug excreted in the bile and from the kidney (temocapril hydrochloride, Acecol®) and another ACE inhibitor excreted from the kidney (lisinopril, Longes®) using the models. In the temocapril dosed groups, the elimination rate constant (Ke, 1/hr) was 1.03 for the hepatic disorder model group and 0.15 for the cholestatic model group, and both were significantly smaller than the 1.58 rate constant for the control group. Although no significant difference was noted, the renal disorder model group showed a slightly decreased Ke value of 1.27 compared with the control group. In the lisinopril dosed groups, the half-life was long, and no intergroup difference was observed in the pharmacokinetic parameters until 6 hr after administration. The results of the present study suggest that the use of temocapril is safer when renal disorders occur while the use of lisinopril is safer for hepatic disordes. In order to minimize the development of adverse reactions and to obtain the desired clinical efficacy, it is necessary to select drugs only after sufficiently analyzing the condition of each illness and taking into account the characteristic properties of the individual drugs.