Pharmacokinetics of fosinopril in patients with various degrees of renal function

Abstract

Single-dose kinetics of fosinopril, a new phosphorus-containing angiotensin-converting enzyme inhibitor and its active diacid, fosinoprilat, were investigated in patients with mild, moderate, or severe renal impairment and in those with normal renal function. After an intravenous dose of 14C-fosinoprilat (7.5 mg), total body clearance of fosinoprilat was significantly greater (p less than 0.05) in patients with normal renal function than in renally impaired patients but was not related to the degree of renal impairment in patients with creatinine clearance values of 11 to 72 ml/min/1.73 m2. Decreases in renal clearance were compensated for by increases in hepatic clearance, so that total clearance was maintained. After oral 14C-fosinopril (10 mg), plasma kinetics and bioavailability of fosinoprilat were similar for the three groups of renally impaired patients. The dual elimination of fosinoprilat by the liver and the kidney distinguishes fosinopril from other angiotensin-converting enzyme inhibitors.

Evaluation of antihypertensive effects of once‐a‐day isradipine and fosinopril: A double‐blind crossover study by means of ambulatory blood pressure monitoring

“…As kidney function declines, hepatic mechanisms such as biliary secretion adjust to maintain body clearance of fosinoprilat. 16 As has been reported, a better goal of antihypertensive therapy might be to reduce BPL in addition to MBP because BPL may play a more important role than MBP in target-organ damage such as left ventricular hypertrophy. A BPL of 15% has been proposed as the upper limit in normotensive subjects.I7 Our data show that FOS is more effective than ISR in the lowering of both systolic and diastolic BPL (Fig.…”

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

“…Because of the lack of sensitive determining method, it has never been reported to study pharmacokinetics of fosinopril in human being [6][7][8][9][10][18][19][20]. The present method makes it possible to determine the concentration changes of fosinopril as time changes and therefore could reveal the characters of fosinopril.…”

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

“…Эти свойства фозиноприла с успехом используют при лечении пациентов пожилого АРТЕРИАЛЬНАЯ ГИПЕРТЕНЗИЯ возраста, с коморбидной патологией, в частности с сахар-ным диабетом (СД), у которых возможно снижение функ-ционального состояния почек и печени [6]. По данным специальных фармакокинетических исследований, у пациентов с циррозом печени экскреция фозиноприлата с мочой возрастает в 1,5-2 раза по сравнению со здоро-выми лицами, у больных с почечной недостаточностью в 2-3 раза усиливается печеночный путь выведения [7].…”