Single dose and steady state pharmacokinetics of temocapril and temocaprilat in young and elderly hypertensive patients

AIMS: The aim of this study was to determine the potential impact of age on the pharmacokinetics of temocapril and its pharmacologically active diacid metabolite, temocaprilat, in hypertensive patients. METHODS: Male and female patients with mild to moderate essential hypertension (DBP 95-114 mmHg inclusive) were allocated to two age groups: young, < or = 40 years; elderly, > or = 69 years, (n = 18 per group). In Part I of the study, subjects took a single oral tablet dose of 20 mg temocapril hydrochloride following an overnight fast. In Part II they took seven once daily oral tablet doses of 20 mg temocapril hydrochloride. Pharmacokinetic profiles were determined after the single and the last dose. Trough plasma samples were taken before each dose in Part II. Urine was collected for 24 h following the single and the last dose. RESULTS: Steady state was reached within 1 week in both groups. Statistically significant differences were detected in AUC and AUCss for temocaprilat as well as in CL(R) for temocapril and temocaprilat, respectively, after a single dose and at steady state. All other pharmacokinetic parameters for temocapril and temocaprilat did not show any significant difference. CONCLUSIONS: The pharmacokinetic differences detected in the elderly do not require a dose adjustment per se. Nonetheless, a lower starting dose may be appropriate as elderly hypertensive patients are usually considered to be at an increased risk of first dose hypotension at the onset of treatment with an ACE inhibitor.