Pharmacokinetics of Midazolam and 1′-Hydroxymidazolam in Chinese with Different CYP3A5 Genotypes

Shih, Pei-Shan; Huang, Jin‐ding

doi:10.1124/dmd.30.12.1491

Cited by 129 publications

(101 citation statements)

References 22 publications

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“…Interestingly, a similar result has been obtained in the case of midazolam, a typical CYP3A5 substrate. Namely, midazolam pharmacokinetics was also hardly influenced in vivo by the genotype of CYP3A5, 18 although midazolam is metabolized in vitro by CYP3A5 rather than CYP3A4. 3,17,19 Several possibilities can be proposed to explain these discrepancies between the in vitro and in vivo data.…”

Section: Discussionmentioning

confidence: 99%

CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers

et al. 2003

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CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5*1/*3; eight subjects: CYP3A5*3/*3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C max ) and the terminal half-life (t 1/2 ) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials. 2 Recently, single-nucleotide polymorphisms (SNPs) were identified in intron 3 (A-G: CYP3A5*3) and exon 7 (G-A: CYP3A5*6) of the CYP3A5 gene.3 In addition, CYP3A5*5 and CYP3A5*7 were reported as a defective allele of CYP3A5, which gave a substantial impact on CYP3A5 expression. 4,5 These SNPs cause a frame-shift mutation or alternative splicing and protein truncation, and result in the absence of CYP3A5, suggesting that only people with at least one CYP3A5*1 allele express large amounts of CYP3A5 protein. Therefore, these findings suggest that polymorphic CYP3A5 expression might be one factor contributing to the marked interindividual variation observed in CYP3A-mediated metabolism of drugs.We previously reported the frequencies of CYP3A5-related SNPs in 200 healthy Japanese subjects. 6 As a result, the allele frequency of CYP3A5*3 was approximately 70%, but CYP3A5*6 was not detected in the Japanese population. Accordingly, these findings suggested that about 40% of Japanese express relatively high levels of metabolically active CYP3A5 protein.

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Section: Discussionmentioning

confidence: 99%

CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers

et al. 2003

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“…Results of PAGE are illustrated in Fig. 2. CYP3A4 isoenzymes are responsible for the metabolism of > 50% of drugs such as steroid components, antidepressant, antibiotics, ... [4]. Pharmacogenetic studies show that genetic variations in this gene and other genes of CYP450 superfamily (specially polymorphism) can affect metabolism process of drugs [1].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, CYP3A4 enzyme product is responsible for over 50% of all clinically drug products [3]. These drugs are included steroids immunosuppressive agent [4]. Also, CYP3A4 is responsible for the conversion of testosterone to less biologically active forms of this hormone, such as 2β, 6β, and 15β-hydroxy testosterone [5].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the CYP3A4*1B Gene Variant in an Iranian Population: Pilot Base Study

Zahmatkesh

Movafagh

2015

IJPPE

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ABSTRACT. Various studies revealed that, CYP3A4*1B, as a variant allele of CYP3A4 gene, has variations in populations with different ethnic background. In this pilot research work, we studied 183 healthy non consanguinity men of an Iranian origin for this genetic variation. We applied RFLP-PCR technique for this research study. In contrast with other researches, in Asian country (such as China and Japan with 0% allele frequency) our study showed that frequency of this allele in Iranian men among an Asian continent is 3%. This finding is an important attempt in pharmacogenetics research endeavor.

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“…Kuehl et al [11] showed that G/A (44 polymorphism in CYP3AP1 was linked to the splicing defect of CYP3A5*3/*1. Shih et al [12] also showed that G/A (44 polymorphism of CYP3AP1 promoter has strong association with a/g 22893 polymorphism in intron 3 of CYP3A5 in Chinese. Both of them showed that the patients carrying CYP3AP1*1 also carried CYP3A5*1, in the same way, patients carrying CYP3AP1*3 also carried CYP3A5*3 and patients carrying CYP3AP1*1/*3 also carried CYP3A5*1/*3.…”

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confidence: 99%