Single-Dose Pharmacokinetics of Nateglinide in Subjects with Hepatic Cirrhosis

• Published in: Journal of clinical pharmacology Vol. 40; no. 6; pp. 634 - 640
• Main Authors: Choudhury, Somesh, Hirschberg, Yulia, Filipek, Ronald, Lasseter, Kenneth, McLeod, James F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2000; Sage Science
• Subjects: Adult; Aged; Biological and medical sciences; Cyclohexanes - administration & dosage; Cyclohexanes - adverse effects; Cyclohexanes - pharmacokinetics; Female; Hormones. Endocrine system; Humans; Hypoglycemic Agents - pharmacokinetics; Liver Cirrhosis - metabolism; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phenylalanine - administration & dosage; Phenylalanine - adverse effects; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacokinetics; Human; Cirrhosis; Hypoglycemic agent; Single dose; Oral administration; Digestive diseases; Hepatic disease; Pharmacokinetics; Nateglinide
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1002/j.1552-4604.2000.tb05989.x

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.