OBJECTIVE: To evaluate the pharmacokinetic profiles of temocaprilat and its hypotensive effect after single and repeated dosings of temocapril in young and elderly hypertensive patients. METHODS: An angiotensin-converting enzyme inhibitor, temocapril (2 mg), was given once daily for 8 days to nine young and ten elderly hypertensive patients. Pharmacokinetics of temocaprilat, an active metabolite, and its hypotensive effect were evaluated after the first and last doses. RESULTS: The area under the plasma concentration-time curve (AUC) of temocaprilat after the first dose was significantly greater in the elderly than in the young. This parameter was elevated after the final dose in both groups. The AUC (eighth dose)/AUC (first dose) ratio in the elderly was similar to that in the young. Blood pressure (BP) tended to decrease in the young and significantly decreased in the elderly after the first dose. The hypotensive effect was not enhanced after the final dose in either group. CONCLUSION: These results suggest that although plasma temocaprilat concentration rises during repeated dosing, its BP-lowering effect is not enhanced in the elderly. Therefore, if a remarkable BP reduction is not detected at the initiation of treatment, the risk of hypotensive episode might be small during long-term therapy with temocapril in elderly hypertensive patients.
OBJECTIVE: To evaluate the pharmacokinetic profiles of temocaprilat and its hypotensive effect after single and repeated dosings of temocapril in young and elderly hypertensivepatients. METHODS: An angiotensin-converting enzyme inhibitor, temocapril (2 mg), was given once daily for 8 days to nine young and ten elderly hypertensivepatients. Pharmacokinetics of temocaprilat, an active metabolite, and its hypotensive effect were evaluated after the first and last doses. RESULTS: The area under the plasma concentration-time curve (AUC) of temocaprilat after the first dose was significantly greater in the elderly than in the young. This parameter was elevated after the final dose in both groups. The AUC (eighth dose)/AUC (first dose) ratio in the elderly was similar to that in the young. Blood pressure (BP) tended to decrease in the young and significantly decreased in the elderly after the first dose. The hypotensive effect was not enhanced after the final dose in either group. CONCLUSION: These results suggest that although plasma temocaprilat concentration rises during repeated dosing, its BP-lowering effect is not enhanced in the elderly. Therefore, if a remarkable BP reduction is not detected at the initiation of treatment, the risk of hypotensive episode might be small during long-term therapy with temocapril in elderly hypertensivepatients.