Nateglinide is an anti-diabetic drug that belongs to the meglitinide category. It helps to lower blood glucose levels by blocking ATP-dependent potassium channels in pancreatic beta cells, which in turn, stimulates insulin secretion. Similar to repaglinide, nateglinide also has a rapid onset and short duration of action. It has been used alone or in combination with other medications to treat patient with type 2 diabetes.
Nateglinide is administered 0-30 minutes before meals as a meal time glucose regulator. It is rapidly absorbed from the gastrointestinal tract and undergoes extensive biotransformation in liver to at least nine metabolites. Of the 9 metabolites, the majority of them are hydroxylation products with M1 as the predominant metabolite which is monohydroxylated at the methane carbon. These major metabolites have much less anti-diabetic activity than nateglinide. The only metabolite that possesses significant pharmacological activity is the isoprene metabolite M7. However, due to low abundance of M7 (<7%), the vast majority of the pharmacological effect is attributed to the parent compounds. Nateglinide is excreted predominantly in urine as metabolites, with only 16% of the dose excreted unchanged. In vitro inhibition experiments with human hepatic microsomes and recombinant human cytochrome P450s suggest the involvement of mainly CYP2C9, and to a lesser extent CYP3A4, in nateglinide metabolism. Patients carrying the CYP2C9*3 alleles have significantly reduced clearance of nateglinide and may have increased risk for hyperglycemia. Similar to repaglinide, genetic polymorphism in hepatic-uptake transporter SLCO1B1 (OATP1B1) is another independent determinant of the pharmacokinetics of nateglinide.
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
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|Arrow From||Arrow To||Controllers||PMID|
|nateglinide||M1||CYP2C9, CYP3A4||11259325, 14748619, 16372821|
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