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  1. Ruzilawati AB, Mohd Suhaimi AW, Gan SH
    J Clin Pharm Ther, 2010 Feb;35(1):105-12.
    PMID: 20175819 DOI: 10.1111/j.1365-2710.2009.01042.x
    To estimate population pharmacokinetic parameters of repaglinide in 121 healthy Malaysian volunteers.
    Matched MeSH terms: Carbamates/pharmacokinetics*
  2. Ruzilawati AB, Wahab MS, Imran A, Ismail Z, Gan SH
    J Pharm Biomed Anal, 2007 Apr 11;43(5):1831-5.
    PMID: 17240100
    In this study, the development and validation of a high-performance liquid chromatography (HPLC) assay for determination of repaglinide concentration in human plasma for pharmacokinetic studies is described. Plasma samples containing repaglinide and an internal standard, indomethacin were extracted with ethylacetate at pH 7.4. The recovery of repaglinide was 92%+/-55.31. Chromatographic separations were performed on Purospher STAR C-18 analytical column (4.8 mm x 150 mm; 5 microm particle size). The mobile phase composed of acetonitrile-ammonium formate (pH 2.7; 0.01 M) (60:40, v/v). The flow rate was 1 ml/min. The retention time for repaglinide and indomethacin were approximately 6.2 and 5.3 min, respectively. Calibration curves of repaglinide were linear in the concentration range of 20-200 ng/ml in plasma. The limits of detection and quantification were 10 ng/ml and 20 ng/ml, respectively. The inter-day precision was from 5.21 to 11.84% and the intra-day precision ranged from 3.90 to 6.67%. The inter-day accuracy ranged 89.95 to 105.75% and intra-day accuracy ranged from 92.37 to 104.66%. This method was applied to determine repaglinide concentration in human plasma samples for a pharmacokinetic study.
    Matched MeSH terms: Carbamates/pharmacokinetics*
  3. Ruzilawati AB, Gan SH
    Pharmacology, 2010;85(6):357-64.
    PMID: 20523106 DOI: 10.1159/000302731
    AIM: To investigate the effects of CYP3A4 and CYP2C8 enzymes on repaglinide's pharmacokinetics in healthy Malaysian subjects.

    METHODS: Subjects (n = 121) received oral repaglinide (4 mg). Blood samples were taken at 0, 30, 60, 120, 180 and 240 min and serum concentrations of repaglinide were determined using high-performance liquid chromatography. Subjects were also genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for CYP3A4*4, *5 and*18 and by an allele-specific multiplex PCR for CYP2C8*2, *3, *4 and *5 alleles.

    RESULTS: The allele frequencies of CYP2C8*1, *2, *3, *4 and *5 were 95.04, 0.40, 0.40, 0 and 4.13%, respectively. The frequencies of the CYP3A4*1, *4, *5 and *18 alleles were 97.93, 0, 0 and 2.07%, respectively. CYP2C8 and CYP3A4 genotypes were not significantly associated with repaglinide's blood glucose-lowering effect. However, the CYP3A4 genotype significantly influenced some of repaglinide's pharmacokinetics, where the mean elimination rate constant was 44.0% lower (p = 0.04) and the mean half-life was 33.8% higher (p = 0.04) in subjects with the CYP3A4*1/*18 genotype as compared to those with the normal CYP3A4*1/*1 genotype. This result confirms that CYP3A4 plays a large role in metabolizing repaglinide.

    CONCLUSION: Genetic polymorphisms of CYP3A4, specifically CYP3A4*18, play a major role in contributing to the interindividual variability in repaglinide's pharmacokinetics.

    Matched MeSH terms: Carbamates/pharmacokinetics*
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