Cody R J
Department of Medicine, Ohio State University, College of Medicine and Hospitals, Columbus.
Clin Pharmacokinet. 1993 Jan;24(1):59-70. doi: 10.2165/00003088-199324010-00005.
Pharmacokinetic studies are often used to provide additional information regarding the use of pharmacological agents for the treatment of cardiovascular disorders. Pharmacokinetic data are available for the major angiotensin converting enzyme (ACE) inhibitors. However, practical guidelines regarding dosage and dosage intervals are not feasible, and measurements of serum drug concentrations are generally not useful in practice. Such use is obscured by the nature of enzymatic inhibition, renin and angiotensin I accumulation, the complex interaction of several organ systems, the compromise of organ system function due to the heart failure process, the effect of ACE inhibitors on other vasoactive substances and the cellular actions of carboxypeptidase (the enzyme otherwise known as ACE). Pharmacodynamic data demonstrate 2 important factors that influence ACE inhibitor pharmacokinetics and serum concentrations: the aging process and abnormal renal function. As most patients with moderate to severe heart failure have reduced renal function, this has practical implications. Furthermore, heart failure is common in the elderly, and even within the population with heart failure, a superimposed further reduction in renal function can be identified in elderly patients with heart failure. Therefore, a more careful analysis of ACE inhibitor dosage must be made in the presence of decreased renal function and in the elderly patient with heart failure.
药代动力学研究常被用于提供有关使用药物治疗心血管疾病的更多信息。主要的血管紧张素转换酶（ACE）抑制剂已有药代动力学数据。然而，关于剂量和给药间隔的实用指南并不可行，而且血清药物浓度的测量在实际中通常并无用处。酶抑制的性质、肾素和血管紧张素I的蓄积、多个器官系统的复杂相互作用、心力衰竭过程导致的器官系统功能受损、ACE抑制剂对其他血管活性物质的影响以及羧肽酶（即所谓的ACE）的细胞作用使这种应用变得模糊不清。药效学数据表明有两个重要因素会影响ACE抑制剂的药代动力学和血清浓度：衰老过程和肾功能异常。由于大多数中重度心力衰竭患者肾功能减退，这具有实际意义。此外，心力衰竭在老年人中很常见，而且即使在心力衰竭患者群体中，老年心力衰竭患者的肾功能也会进一步降低。因此，在肾功能减退和老年心力衰竭患者中，必须更仔细地分析ACE抑制剂的剂量。
