Single-dose pharmacokinetics of repaglinide in subjects with chronic liverdisease

Repaglinide is a novel insulin secretagogue developed in response to the ne ed for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolize d mainly in the liver; its pharmacokinetics may therefore be altered by hep atic dysfunction. This open, parallel-group study compared the pharmacokine tics and tolerability of a single 4 mg dose of repaglinide in healthy subje cts (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and C-max were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for t(m ax) did not differ between the groups, but t(1/2) was significantly prolong ed in CLD patients compared with previously determined values in healthy su bjects. AUC was inversely correlated with caffeine clearance in CLD patient s but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two g roups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group. Journal of Clinical Pharmacology, 2000;40:142-152 (C)2000 the A merican College of Clinical Pharmacology.