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 ag e on the pharmacokinetics of temocapril and its pharmacologically acti ve 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, l ess than or equal to 40 years; elderly, greater than or equal to 69 ye ars, (n=18 per group). In Part I of the study, subjects took a single oral tablet dose of 20 mg temocapril hydrochloride following an overni ght fast. In Part II they took seven once daily oral tablet doses of 2 0 mg temocapril hydrochloride. Pharmacokinetic profiles were determine d 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 t he single and the last dose. Results Steady state was reached within 1 week in both groups. Statistically significant differences were detec ted in AUC and AUC(ss) for temocaprilat as well as in CLR for temocapr il and temocaprilat, respectively, after a single dose and at steady s tate. Ail other pharmacokinetic parameters for temocapril and temocapr ilat did not show any significant difference. Conclusions The pharmaco kinetic differences detected in the elderly do not require a dose adju stment per re. Nonetheless, a lower starting dose may be appropriate a s elderly hypertensive patients are usually considered to be at an inc reased risk of first dose hypotension at the onset of treatment with a n ACE inhibitor.