Moexipril显示了一个长期的行动与延长药代动力学半衰期和长时间的ACE抑制。

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Cawello W, Boekens H, Waitzinger J,米勒U

Moexipril显示了一个长期的行动与延长药代动力学半衰期和长时间的ACE抑制。

Int中国新药杂志。2002年1月,40(1):上行线。

PubMed ID

11837383 (在PubMed

]

文摘

目的:描述亲脂性的血管紧张素转化酶抑制剂moexipril及其活性代谢物moexiprilat关于行动的持续时间,药物动力学和药效学的易感性食物摄取和浓度效应。方法:三个独立、开放、随机研究在健康受试者使用交叉或与这些相应平行的组织设计。在第一项研究中,药物动力学(AUC, Cmax、达峰时间t 1/2)和ACE抑制(72小时)后进行单一口服剂量的15毫克moexipril管理在空腹和餐后状态(n = 24)。个人ACE抑制数据和血浆浓度数据被安装在一个Emax模型。在第二项研究中,在52名志愿者,药物动力学进行随访超过36小时后管理moexipril 2单一口服剂量的15毫克。在第三个研究中,药物动力学在多次给药15毫克moexipril曾经连续5天每天12年轻人和12老年人进行调查。结果:Moexiprilat达峰时间为1.5 2 h单个和多个剂量之间只有细微的差别。相比,空腹、餐后moexiprilat Cmax和AUC(比美联储/禁食58.0%;90%可信区间52.2 - -64.5%)明显降低(方差分析p = 0.0001)。Moexiprilat显示两相的消除阶段平均半衰期29 - 30日相h。相比之下,在终端消除阶段血浆浓度不受食物的影响。 A relationship between ACE inhibition and plasma concentration was not observed. The average ACE inhibition over 72 h was 71 % in the fasting state and 74% in the postprandial state. ACE inhibition increased to about 80% after 24 h and decreased to about 60% at 72 h. The S-shaped concentration-effect curve indicated that a moexiprilat level of 1.3 ng/ml was sufficient to produce 50% inhibition of ACE. With repeated dosing there were no signs of drug accumulation and day-to-day drug levels were relatively constant. The trough concentrations at 24 h did not fall below the limit of 1-2 ng/ml, i.e. a 50% ACE inhibition. CONCLUSION: Moexiprilat showed an extended duration of action owing to a long terminal pharmacokinetic half-life and produced a persistent ACE inhibition. Although the pharmacokinetics were partly influenced by food intake, ACE inhibition was not affected. This might be explained by a second compartment directly related to the ACE which is less prone to food effects and the reaching of a ceiling in the sigmoidal concentration-effect curve even with the lower Cmax concentrations associated with the postprandial state.

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药物

Moexipril