Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine sustained-release tablets.

Abstract:

:The effect of hepatic impairment on the pharmacokinetics of a sustained-release formulation of ranolazine and 3 major metabolites was investigated in an open-label, parallel-group study. Ranolazine (875-mg loading dose followed by 500 mg every 12 hours for a total of 4 maintenance doses) was administered to subjects with mild (n = 8) or moderate (n = 8) hepatic impairment and a matched control group of healthy volunteers (n = 16). Moderate, but not mild, hepatic impairment significantly increased ranolazine steady-state area under the concentration-time curve (AUC0-12) by 76% (P < .001) and maximum plasma concentration C(max) by 51% (P < .01). The AUC0-12 ratio (metabolite/ranolazine) decreased for all metabolites in parallel with the degree of hepatic impairment. AUC0-infinity for the CYP3A substrate midazolam administered as a single dose was significantly correlated with ranolazine AUC0-12 at steady state (r2 = .33, P < .001). Over the time interval studied, ranolazine was well tolerated in healthy subjects and hepatically impaired subjects.

journal_name

J Clin Pharmacol

authors

Abdallah H,Jerling M

doi

10.1177/0091270005276739

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

802-9

issue

7

eissn

0091-2700

issn

1552-4604

pii

45/7/802

journal_volume

45

pub_type

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