Single-point plasma or urine dextromethorphan method for determining CYP3A activity

Benjamin Pei-Chung Kuo, Oliver Yoa-Pu Hu, Cheng Huei Hsiong, Li Heng Pao, Ting Shien Chen, Chi Feng Hung

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

Dextromethorphan is used widely in vivo to phenotype the polymorphically expressed cytochrome P450 (CYP) 2D6. Also dextromethorphan is N-demethylated in vivo to 3-methoxymorphinan by human CYP3A4/5. The metabolic ratio (MR) of dextromethorphan/3-methoxymorphinan in plasma, saliva and urinary were examined as a possible in vivo probe of CYP3A activity. In limited previous studies, 4 h urinary samples were collected for determining the MR. To evaluate the repeatability and validity of previously reported and other potential phenotyping methods, the MR from urine samples (at various intervals), from plasma and from saliva (at varying time points) were determined after repetitive single doses of immediate-release or repetitive multiple doses of controlled-release dextromethorphan preparations. For the single-dose study, each of 12 subjects received 15 mg of immediate-release dextromethorphan in periods II and I, respectively, with a 1 week washout period. For the multiple dose study, each of 16 subjects received 60 mg controlled release dextromethorphan twice daily for 5 days in periods I and II, respectively, with a 2 week washout period. Dextromethorphan and 3-methoxymorphinan are assayed by high-performance liquid chromatography. In the single-dose study, all of the urine MR revealed good repeatabilities for the periods (paired t-test). The urine MR at any time interval of 0-6 h, 0-8 h and 0-12 h correlated significantly with the MR from 0-24 h urine (r>0.8, p<0.05). In the multiple-dose study, an MR revealed good repeatabilities for the two periods (paired t-test). The plasma MR at any time between 0.5 h and 12 h, the saliva MR at 12 h and the urine MR at any interval between 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h and 0-24 h could predict the MR from AUC τ ss . In conclusion, the urine sample as 0-6 h, 0-8 h or 0-12 h in the single immediate-release dose (15 mg) or in the multiple controlled-release dose (60 mg) procedure, the saliva sample at 12 h, the urine sample at 0-2 h, 0-4 h, 0-6 h, 0-8 h, 0-12 h, 0-24 h or all plasma-sampling points 0.5-12 h could be used as the dextromethorphan MR for determining the CYP3A activity.
原文英語
頁(從 - 到)367-373
頁數7
期刊Biopharmaceutics and Drug Disposition
24
發行號9
DOIs
出版狀態已發佈 - 十二月 1 2003
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

引用此

Pei-Chung Kuo, B., Yoa-Pu Hu, O., Hsiong, C. H., Pao, L. H., Chen, T. S., & Hung, C. F. (2003). Single-point plasma or urine dextromethorphan method for determining CYP3A activity. Biopharmaceutics and Drug Disposition, 24(9), 367-373. https://doi.org/10.1002/bdd.373