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Single‐Dose Pharmacokinetics of Nateglinide in Subjects with Hepatic Cirrhosis
Author(s) -
Choudhury Somesh,
Hirschberg Yulia,
Filipek Ronald,
Lasseter Kenneth,
McLeod James F.
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.2000.tb05989.x
Subject(s) - nateglinide , pharmacokinetics , cirrhosis , medicine , tolerability , renal function , adverse effect , pharmacology , gastroenterology , endocrinology , type 2 diabetes , diabetes mellitus
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 (C max , 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.