Single-Dose Pharmacokinetics of Nateglinide in Subjects with Hepatic Cirrhosis

Abstract

This single-dose, open-label, parallel-group study compared the pharmacokinetics and tolerability of 120 mg doses of nateglinide, a physiologic mealtime glucose regulator for type 2 diabetes, in 8 subjects with cirrhosis ande matched healthy subjects. In both groups, plasma concentration peaked in a median of 0.5 hours, and mean terminal elimination half-lives were comparable. Mean ± SD pharmacokinetic parameters in cirrhotic versus healthy subjects were slightly different (Cmax, 7.7 ± 4.9 vs. 5.6 ± 1.3 μg/ml; AUC(0-t), 18.5 ± 7.5 vs. 14.2 ± 2.1 μg·h/ml, respectively). Mean apparent total clearance and mean renal clearance in both groups were comparable. Mean protein-bound fractions were equivalent; binding appeared unaltered by metabolites. One cirrhotic and 2 healthy subjects each reported one adverse event. No statistically significant or clinically relevant alteration in pharmacokinetic parameters of nateglinide resulted from hepatic dysfunction, and it was well tolerated; therefore, adjustment of nateglinide dosage is not required in subjects with mild to moderate cirrhosis.