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Impact of Disease States on the Pharmacokinetics and Pharmacodynamics of Angiotensin-Converting Enzyme Inhibitors

From the College of Pharmacy at The Ohio State University, Columbus, Ohio (Dr LeBlanc, Mr Dasta, Dr Pruchnicki), and the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, and the Clinical Pharmacokinetics Laboratory, University at Buffalo, Buffalo, New York (Dr Schentag).

The pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors (ACE) in elderly patients and patients with renal and hepatic impairment were examined, and a role for an AUC/EC₅₀ ratio to guide dosing was evaluated. A Medline and International Pharmaceutical Abstracts search was used to identify human studies and abstracts. Relevant data were evaluated and summarized. Dosing regimens were compared using an AUC/EC₅₀ ratio. Most studies evaluating ACE inhibitors in renal impairment report a strong linear correlation between creatine clearance and drug elimination. AUC and EC₅₀ values for these drugs in elderly subjects appear similar to younger and hypertensive patients. There is increased AUC in some patients with hepatic impairment. Pharmacodynamic data are conflicting. Prolonged ACE inhibition is evident in renal impairment but not necessarily other disease states. ACE inhibitor dosing for hypertension is reasonable based on pharmacokinetics and EC₅₀ values. Further individualization of therapy may improve outcomes, and using the threshold AUC/EC₅₀ ratio may help guide appropriate dosing.

Key Words: Angiotensin-converting enzyme inhibitors • elderly • renal dysfunction • hepatic dysfunction • review

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