Pharmacokinetic Profiles of Single and Repeat Doses of Lisinopril and Enalapril in Congestive Heart Failure Dennis Johnston,

MD, FRCP,

T

to determine his study was undertaken whether the presence of congestive heart failure (CHF) would alter absorption, firstpass metabolism, and drug elimination and result in different pharmacokinetic profiles for lisinopril and enalapril. Lisinopril is pharmacologically active after oral administration and does not require hepatic activation. Bioavailability is low and the time to peak concentration is prolonged, mainly due to poor absorption. The drug undergoes renal elimination and has a duration effect of > 24 hours.’ Enalapril is a prodrug that requires conversion in the liver to its active form, enalaprilat. Enalaprilat is then excreted by the kidney and has a duration effect of about 24 hours.2 METHODS This was an open, randomized, parallel-group study in 13 patients (2 18 years) with CHF (New York Heart Association class III-IV) on background therapy of diuretics and/or digoxin. Male and female patients were included in the study and the diagnosis of CHF was established when at least 2 of the following features were present: increased jugulovenous pressure, peripheral edema, tender hepatomegaly, or radiologic signs of pulmonary edema. Exclusion criteria were recent myocardial infarction or stroke, aortic stenosis, primary right heart failure, systolic blood pressure 57. 4. Biollaz J, Schellmg JL, Jacot Des Combes B, Brunner DB, Bmnner HR, Desponds G, Ulm EH, Hichens M, Gomez HJ. Enalapril maleate and a lysine analogue (MK521) in normal volunteers; relationship between plasma drug levels md the renin angiotensin system. Br J ain Phamtacol 1982;14:363-

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5. Milk J& Derlot FHM, McLean K, Reid JL. Pharmacodymamics of converting enzyme inhibition: the cardiovascular endocrine and autocrine effects of MK421 (enalapril) and MK521. BrJ Clin Pharmacol1982;14:347-355, 6. Uhn EH, Hichens M, Gomez HJ, Till AE, Hand E, Vassil TC, Biollaz J, Brmmer HR, Schellmg JL. Enalapril maleate and lysine analogue (MK521): disposition in man. Br J Clin Pharmacol1982;14:357-362.

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Pharmacokinetic profiles of single and repeat doses of lisinopril and enalapril in congestive heart failure.

Pharmacokinetic Profiles of Single and Repeat Doses of Lisinopril and Enalapril in Congestive Heart Failure Dennis Johnston, MD, FRCP, T to determi...
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