Single-dose and steady-state pharmacokinetics of fosinopril and fosinoprilat in patients with hepatic impairment
| Autor: | Ralph H. Raymond, Neville F. Ford, Janis L. Hammett, James Manning, Donald R. Van Harken, Kenneth C. Lasseter |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Alcoholic liver disease medicine.medical_specialty Cirrhosis Metabolic Clearance Rate Pharmacokinetics Oral administration Liver Cirrhosis Alcoholic Fosinopril Internal medicine Fosinoprilat medicine Humans Pharmacology (medical) Prodrugs Antihypertensive Agents Pharmacology business.industry Middle Aged medicine.disease Endocrinology Renal physiology Creatinine ACE inhibitor Female business medicine.drug |
| Zdroj: | Journal of clinical pharmacology. 35(2) |
| ISSN: | 0091-2700 |
| Popis: | The single-dose and steady-state pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitor fosinopril and its active diacid, fosinoprilat, were evaluated in 6 healthy volunteers and 12 patients with alcoholic cirrhosis. Fosinopril was administered at a dosage of 10 mg once daily for 14 days. Results in the two groups were similar, with no evidence of accumulation of fosinoprilat in hepatically impaired patients. Mean (+/- SD) maximum observed plasma concentrations of fosinoprilat in the healthy subjects were 112.0 +/- 67.2 ng/mL after the first dose and 144.1 +/- 61.7 ng/mL at steady-state. Corresponding values for the hepatically impaired patients were 111.4 +/- 40.1 ng/mL and 140.2 +/- 50.9 ng/mL. The area under the serum concentration versus time curve for healthy volunteers was 790.7 +/- 431.0 ng.hr/mL after the first dose and 940.3 +/- 400.4 ng.hr/mL at steady-state. Similar values were noted in hepatically impaired patients: 926.0 +/- 293.9 ng.hr/mL and 1,255.4 +/- 434.0 ng.hr/mL for first dose and steady-state, respectively. No statistically significant differences were detected in fosinoprilat pharmacokinetic values between healthy and hepatically impaired subjects. Absence of accumulation can be attributed to the dual route of elimination of fosinoprilat reported in previous studies. Renal excretion of fosinoprilat in hepatically impaired patients prevents increased accumulation. The present findings suggest that the starting dose of fosinopril used in hypertensive patients with normal renal and hepatic function can also be used in patients with hepatic impairment secondary to cirrhosis. |
| Databáze: | OpenAIRE |
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