Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: Possible effect of age, liver disease and length of therapy

Miyuki Kimura, Ichiro Ieiri, Yukiko Wada, Kohsuke Mamiya, Akinori Urae, Emiko Iimori, Terufumi Sakai, Kenji Otsubo, Shun Higuchi

研究成果: ジャーナルへの寄稿学術誌査読

39 被引用数 (Scopus)

抄録

Aims. To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). Methods. Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. Results. In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (≥ 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. Conclusion. Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients.

本文言語英語
ページ(範囲)115-119
ページ数5
ジャーナルBritish journal of clinical pharmacology
47
1
DOI
出版ステータス出版済み - 1999
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬理学(医学)

フィンガープリント

「Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: Possible effect of age, liver disease and length of therapy」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル