Different Effects of <i>SLCO1B1</i> Polymorphism on the Pharmacokinetics and Pharmacodynamics of Repaglinide and Nateglinide

Kalliokoski, Annikka; Neuvonen, Mikko; Neuvonen, Pertti J.; Niemi, Mikko

doi:10.1177/0091270007311569

Cited by 85 publications

(17 citation statements)

References 47 publications

(138 reference statements)

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“…The notion of rosiglitazone as a putative OATP1B1 substrate was further strengthened by existing drug-drug interaction data showing that rosiglitazone concentrations were increased following administration of gemfibrozil, which has both OATP1B1- and CYP2C8-inhibitory actions [34]. Polymorphisms in SLCO1B1 , particularly 521 T > C, have been shown significantly to alter the pharmacokinetics of substrates such as pravastatin and repaglinide [28-30]. Therefore, it can be hypothesised that if rosiglitazone is indeed an OATP1B1 substrate, plasma drug exposure would be higher in subjects carrying a variant SLCO1B1 521C allele, as a result of diminished substrate uptake in the liver.…”

Section: Discussionmentioning

confidence: 99%

Influence of SLCO1B1 and CYP2C8gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Influence of SLCO1B1 and CYP2C8gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers

et al. 2008

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“…A meta-analysis in East Asians confirmed that KCNQ1 rs2237892 was the polymorphism most strongly associated with T2DM susceptibility9. In addition, KCNQ1 also influences the efficacy of repaglinide; however, the underlying mechanisms remain unclear101112. A clinical study demonstrated that diabetic patients with the KCNQ1 rs2237892 T allele were more likely to have a positive response to repaglinide, while patients with the KCNQ1 rs2237892 C allele exhibited larger increases in HOMA-IR13.…”

mentioning

confidence: 98%

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

Zhou

Zhu

Bao

et al. 2016

Sci Rep

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Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).

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“…Pharmacokinetics of both of these glinide drugs is also influenced by variant 521T>C in SLCO1B1 , the gene encoding organic anionic transporter B1 (OATPB1) [15]. …”

Section: Pharmacogenetics Of Insulin Secretagoguesmentioning

confidence: 99%

Pharmacogenetics of Oral Antidiabetic Drugs

Becker

Pearson

Tkáč

2013

International Journal of Endocrinology

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Oral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins constituting ATP-sensitive K+ channel which is a therapeutic target for sulfonylureas, and TCF7L2 is a gene with the strongest association with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant near ATM gene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future.

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Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics and Pharmacodynamics of Repaglinide and Nateglinide

Cited by 85 publications

References 47 publications

Influence of SLCO1B1 and CYP2C8gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers

Influence of SLCO1B1 and CYP2C8gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers

A variation in KCNQ1 gene is associated with repaglinide efficacy on insulin resistance in Chinese Type 2 Diabetes Mellitus Patients

Pharmacogenetics of Oral Antidiabetic Drugs

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