Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers

Yu Cheng, Guo Wang, Wei Zhang, Lan Fan, Yao Chen, Hong-Hao Zhou
European Journal of Clinical Pharmacology 2013, 69 (3): 407-13

PURPOSE: Nateglinide is commonly used in the treatment of patients with type 2 diabetes mellitus. Our objective was to assess the association between CYP2C9 and SLCO1B1 polymorphisms and the metabolism of nateglinide in healthy Chinese male volunteers.

METHODS: A total of 35 healthy Chinese male volunteers with different CYP2C9 and SLCO1B1 genotypes were given a single oral dose of 120 mg nateglinide. Plasma concentrations of nateglinide and blood glucose level were measured up to 8 h.

RESULTS: In subjects with the CYP2C9*1/*3 & 521TT, CYP2C9*1/*1 & 521TC/CC and CYP2C9*1/*3 & 521TC genotype, AUC(0-∞) of nateglinide was 56 %, 34 % and 56 % higher (P = 0.002, P = 0.041 and P = 0.013, respectively), and the CL/F of nateglinide was 35 %, 11 % and 36 % lower (P = 0.000, P = 0.003 and P = 0.002, respectively) than that in the reference group. When only considering 521 T>C polymorphism, it had no significant association with the pharmacokinetics of nateglinide. CYP2C9*3 and 521 T>C polymorphisms were the significant predictors of the AUC(0-∞) and CL/F of nateglinide (adjusted multiple R(2) = 34 % and 43 %, respectively) according to multiple linear regression analyses, but they have no significant association with changes in the blood glucose-lowering effect of nateglinide.

CONCLUSIONS: Both SLCO1B1 521 T>C and the CYP2C9*3 polymorphisms can significantly affect the pharmacokinetics of nateglinide, but they could only partially explain the interindividual variability of plasma concentration of nateglinide. Moreover, 521 T>C and the CYP2C9*3 polymorphisms have no effect on pharmacodynamics of nateglinide in healthy Chinese male subjects.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"