Why the study?
Does hepatic impairment alter the multiple-dose pharmacokinetics of ranolazine sustained-release tablets?
Does hepatic impairment alter the multiple-dose pharmacokinetics of ranolazine sustained-release tablets?
Moderate, but not mild, hepatic impairment significantly increases systemic exposure to ranolazine, suggesting potential need for dose adjustments or caution in this population.
Supports dose caution with ranolazine in moderate hepatic impairment; leaves open outcome effects and mild-impairment data.
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.
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Abdallah et al. (2005) studied this question.
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