Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency

Abstract

Aims To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. Methods Patients with congestive heart failure (CHF, NYHA Class II–IV) and chronic renal insufficiency (creatinine clearance ≤30 ml min−1 ) were randomized to receive fosinopril, enalapril or lisinopril in two parallel‐group studies. In the first study 24 patients were treated with 10 mg fosinopril (n=12 patients) or 2.5 mg enalapril (n=12) every morning for 10 consecutive days. In the second study 31 patients were treated with 10 mg fosinopril (n=16 patients) or 5 mg lisinopril (n=15) every morning for 10 consecutive days. Samples of blood were collected for determination of pharmacokinetic parameters. The area under the curve (AUC) between the first and last days of treatment and the accumulation index (AI) were the primary outcome measures. Results All three angiotensin converting enzyme (ACE) inhibitors exhibited a significant increase in AUC between the first and last days of treatment in both studies. The difference between the AI for fosinoprilat (1.41) and enalaprilat (1.96) was statistically significant (95% CI: 1.05, 1.84). Similarly, the difference between the AI for fosinoprilat (1.21) and lisinopril (2.76) was statistically significant (95% CI: 1.85, 2.69). All three ACE inhibitors completely inhibited serum ACE for 24 h. All treatments were well tolerated. Conclusions Fosinoprilat exhibits significantly less accumulation than enalaprilat or lisinopril in patients with CHF and renal insufficiency, most probably because fosinoprilat is eliminated by both the kidney and liver, and increased hepatic elimination can compensate for reduced renal clearance in patients with kidney dysfunction.

The Place of Fosinopril in Evidence-Based Treatment of Patients With Arterial Hypertension

“…Прямое сравнение фармакокинетики фозиноприла, эналаприла и лизиноприла при назначении однократно в сутки показало, что степень кумуляции фозиноприла через 10 дней от начала применения достоверно ниже, чем лизиноприла и эналаприла [8].…”

Concept and therapeutic approach to cardiorenal insufficiency

“…Naime, fosinopril se značajno manje akumulira u plazmi bolesnika sa HBI u odnosu na enalapril i lizinopril, što je verovatno posledica njegovog dualnog izluči-vanja preko jetre i bubrega. 18 Ova činjenica stvara teoretsku mogućnost da fosinopril ima manju učestalost neželjenih efekata i bolju efikasnost u odnosu na ostale ACEi, ali za sada nema podataka koji bi ovu pretpostavku potvrdili.…”

Development and validation of liquid chromatography–tandem mass spectrometric method for simultaneous determination of fosinopril and its active metabolite fosinoprilat in human plasma

“…Several methods have been reported to determine fosinoprilat in biological fluids [6][7][8][9]11], while all of them have their own disadvantages to analysis of batches of biological samples. Gas chromatography with nitrogen-phosphorus detection (NPD) needed time-consuming derivatization [6].…”