Pharmacokinetics and pharmacodynamics of temocapril during repeated dosing in elderly hypertensive patients
Pharmacokinetics and pharmacodynamics of temocapril during repeated dosing in elderly hypertensive patients
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DOI：
10.1007/s002280000237
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发表时间：
2001-01-01
影响因子：
2.9
通讯作者：
Fujimura, A
中科院分区：
文献类型：
--
作者：
Arakawa, M;Sasaki, M;Fujimura, A
目的：评价替莫普利特在青年和老年高血压患者单次和多次给药后的药动学特征及降压效果。方法：用血管紧张素转换酶抑制剂替莫普利（2 mg）治疗9例青年高血压患者和10例老年高血压患者，每日1次，连用8 d。研究了活性代谢物替莫卡普利特的药代动力学及末次给药后的降压效果。老年人首次给药后替莫卡普利特的血浆浓度-时间曲线下面积（AUC）明显大于年轻人。该参数在两组末次给药后均升高。老年人的AUC（第八剂量）/AUC（第一剂量）比与年轻人相似。首次给药后，年轻人血压有下降趋势，老年人血压明显下降。两组在末次给药后降压效果均未增强。结论：反复给药时，替莫卡普利的血浆浓度升高，但其降血压作用在老年人中并未增强。因此，如果在治疗开始时未检测到明显的血压降低，那么老年高血压患者长期使用替莫普利治疗时发生低血压发作的风险可能很小。
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.