Study on pharmacokinetics of a new biliary excreted oral angiotensin converting enzyme inhibitor, temocapril (CS-622) in humans

Despite the usefulness of angiotensin converting enzyme (ACE; EC 3.4.15.1) inhibitors for patients with renal insufficiency, some hesitation has been exercised in applying ACE inhibitors to the treatment of such patients because most ACE inhibitors are excreted mainly into the urine. In this context, development of an ACE inhibitor which is excreted into the bile has been sought. The pharmacokinetic properties of the novel ACE inhibitor, temocapril hydrochloride (temocapril HCl; CS‐622), were investigated in six healthy volunteers. This drug is excreted mainly into the bile in animal studies. Temocapril HCl was given in a single dose of 0.5, 1.0, and 2.0 mg, and 36, 44, and 38 per cent of the administered drug was excreted in the feces and 17, 19, and 24 per cent in the urine as the de‐esterified active diacid form (the diacid metabolite) within 48 h, respectively. The plasma ACE activity was markedly inhibited. No abnormal clinical findings suggestive of side‐effects were observed. Thus, from the pharmacokinetic standpoint, temocapril HCl is expected to be a useful drug for patients with renal dysfunction.