Comparative pharmacokinetics of captopril, enalapril, and quinapril

This review compares the metabolism and pharmacokinetic profiles of captopril, the first orally active angiotensin-converting enzyme (ACE) inhibitor, and 2 newer ACE inhibitors, enalapril and quinapril. Captopril differs from both enalapril and quinapril in that its chemical structure contains a sulfhydryl group, the presence of which may be important in the development of adverse reactions. Captopril also differs from enalapril and quinapril in its ability to be metabolized in plasma. Enalapril and quinapril are both de-esterified, most likely in the liver, to their active metabolites, enalaprilat and quinaprilat. All 3 ACE inhibitors are eliminated primarily via renal excretion, and renal dysfunction markedly increases the area under the time versus plasma concentration curves. Hepatic dysfunction also slows the conversion of enalapril and quinapril to their active metabolites. There is evidence that both captopril and enalapril, but not quinapril, may accumulate with repeated dosing. The pharmacokinetics of these agents are not significantly modified by co-administration of other drugs. However, captopril does cause marked increases in trough plasma levels of digoxin. Overall, the pharmacokinetic profiles of captopril, enalapril, and quinapril make them suitable for a wide range of patients with hypertension or congestive heart failure.