Arakawa M, Sasaki M, Ohmori M, Harada K, Fujimura A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Eur J Clin Pharmacol. 2001 Jan-Feb;56(11):775-9. doi: 10.1007/s002280000237.
To evaluate the pharmacokinetic profiles of temocaprilat and its hypotensive effect after single and repeated dosings of temocapril in young and elderly hypertensive patients.
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.
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.
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.
评估替莫卡普利在青年和老年高血压患者单次及重复给药后替莫卡普利拉的药代动力学特征及其降压效果。
对9名青年和10名老年高血压患者，每日一次给予血管紧张素转换酶抑制剂替莫卡普利（2毫克），共给药8天。在首次和末次给药后评估活性代谢产物替莫卡普利拉的药代动力学及其降压效果。
首次给药后，替莫卡普利拉的血浆浓度-时间曲线下面积（AUC）在老年患者中显著高于青年患者。两组在末次给药后该参数均升高。老年患者的AUC（第八次给药）/AUC（首次给药）比值与青年患者相似。首次给药后，青年患者血压有下降趋势，老年患者血压显著下降。两组在末次给药后降压效果均未增强。
这些结果表明，尽管重复给药期间血浆替莫卡普利拉浓度升高，但其在老年患者中的降压效果并未增强。因此，如果在治疗开始时未检测到明显的血压降低，老年高血压患者长期使用替莫卡普利治疗期间发生低血压事件的风险可能较小。
