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Influence of UGT genetic polymorphism on the interindividual variability in mitiglinide pharmacokinetic in Chinese

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Abstract

The aim of the study is to identify the effect of UDP-glucuronosyltransferase (UGT) genetic polymorphism on the interindividual variability in mitiglinide pharmacokinetics (PK) in Chinese. PK and genetic data were obtained from 42 healthy Chinese volunteers (Han ethnic group) treated with single-dose and multiple-dose oral mitiglinide using liquid chromatography/mass spectrometry and DNA sequencing technologies. And the result showed there were great interindividual variabilities in main PK parameters (AUC, Cmax and CL/F) for multiple oral mitiglinide. The enzyme activity of the carriers of UGT1A3 *2/*4 or UGT2B7-1 T/T was stronger than that of the carriers of other genotypes. These results demonstrate that UGT1A3 and UGT2B7-1 genetic polymorphism may have a significant impact on interindividual variability in the PK of mitiglinide in Chinese.

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Abbreviations

AUC:

The area under curve

C max :

Maximum concentration

CL/F:

Clearance

MGN:

Mitiglinide

PK:

Pharmacokinetics

UGT:

Uridine 5′-diphospho-glucuronosyltransferase

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Authors and Affiliations

  1. Department of Pharmacology, General Hospital of Beijing Millitary Command, Beijing, 100700, China

    Jing-feng Xu, Zhan-qing Wang, Chen-xia Yan, Qian Xu, Lin Xu, Gang-tao Zhao & Yong-ge Yang

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  1. Jing-feng Xu
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  2. Zhan-qing Wang
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  3. Chen-xia Yan
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  4. Qian Xu
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  5. Lin Xu
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  6. Gang-tao Zhao
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  7. Yong-ge Yang
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Correspondence to Zhan-qing Wang.

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Xu, Jf., Wang, Zq., Yan, Cx. et al. Influence of UGT genetic polymorphism on the interindividual variability in mitiglinide pharmacokinetic in Chinese. Med Chem Res 21, 2595–2602 (2012). https://doi.org/10.1007/s00044-011-9784-0

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  • DOI: https://doi.org/10.1007/s00044-011-9784-0

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