Pharmacokinetics and safety of candesartan cilexetil in subjects with normal and impaired liver function.

Autor: Hoogkamer JF; Takeda Euro Research and Development Centre, Frankfurt am Main, Germany., Kleinbloesem CH, Ouwerkerk M, Högemann A, Nokhodian A, Kirch W, Weidekamm E
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 1998 Jun; Vol. 54 (4), pp. 341-5.
DOI: 10.1007/s002280050471
Abstrakt: Objective: The influence of liver disease on the pharmacokinetics of candesartan, a long-acting selective AT1 subtype angiotensin II receptor antagonist was studied.
Methods: Twelve healthy subjects and 12 patients with mild to moderate liver impairment received a single oral dose of 12 mg of candesartan cilexetil on day 1 and once-daily doses of 12 mg on days 3-7. The drug was taken before breakfast. Serial blood samples were collected for 48 h after the first and last administration on days 1 and 7. Serum was analyzed for unchanged candesartan by HPLC with UV detection.
Results: The pharmacokinetic parameters on days 1 and 7 revealed no statistically significant influence of liver impairment on the pharmacokinetics of candesartan. Following single dose administration on day 1, the mean Cmax was 95.2 ng.ml-1 in healthy subjects and 109 ng.ml-1 in the patients. The AUC0-infinity was 909 ng.h.ml-1 in healthy volunteers and 1107 ng.h.ml-1 in patients and the elimination half-life was 9.3 h in healthy volunteers and 12 h in the patients. At steady state on day 7, mean Cmax values were similar in both groups (112 vs 116 ng.ml-1); the AUC tau was 880 ng.h.ml-1 in healthy subjects and 1080 ng.h.ml-1 in patients while the elimination half-life was 10 h in healthy subjects and 12 h in the patients with liver impairment. The ACU0-infinity on day 1 was almost identical to the AUC tau on day 7. A moderate drug accumulation of 20%, which does not require a dose adjustment, was observed following once-daily dosing in both groups. No serious or severe adverse events were reported.
Conclusion: Mild to moderate liver impairment has no clinically relevant effect on candesartan pharmacokinetics, and no dose adjustment is required for such patients.
Databáze: MEDLINE
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