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

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)367-373
Number of pages7
JournalBiopharmaceutics and Drug Disposition
Volume24
Issue number9
DOIs
Publication statusPublished - Dec 1 2003
Externally publishedYes

Fingerprint

Dextromethorphan
Cytochrome P-450 CYP3A
Urine
Saliva
Delayed-Action Preparations
Cytochrome P-450 CYP2D6
Area Under Curve
High Pressure Liquid Chromatography
Phenotype

Keywords

  • CYP3A activity
  • Dextromethorphan metabolic ratio
  • Plasma ratio
  • Urine ratio

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

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

Single-point plasma or urine dextromethorphan method for determining CYP3A activity. / Pei-Chung Kuo, Benjamin; Yoa-Pu Hu, Oliver; Hsiong, Cheng Huei; Pao, Li Heng; Chen, Ting Shien; Hung, Chi Feng.

In: Biopharmaceutics and Drug Disposition, Vol. 24, No. 9, 01.12.2003, p. 367-373.

Research output: Contribution to journalArticle

Pei-Chung Kuo, B, Yoa-Pu Hu, O, Hsiong, CH, Pao, LH, Chen, TS & Hung, CF 2003, 'Single-point plasma or urine dextromethorphan method for determining CYP3A activity', Biopharmaceutics and Drug Disposition, vol. 24, no. 9, pp. 367-373. https://doi.org/10.1002/bdd.373
Pei-Chung Kuo, Benjamin ; Yoa-Pu Hu, Oliver ; Hsiong, Cheng Huei ; Pao, Li Heng ; Chen, Ting Shien ; Hung, Chi Feng. / Single-point plasma or urine dextromethorphan method for determining CYP3A activity. In: Biopharmaceutics and Drug Disposition. 2003 ; Vol. 24, No. 9. pp. 367-373.
@article{6197be6932904a6eb331387b2fdd0f7b,
title = "Single-point plasma or urine dextromethorphan method for determining CYP3A activity",
abstract = "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.",
keywords = "CYP3A activity, Dextromethorphan metabolic ratio, Plasma ratio, Urine ratio",
author = "{Pei-Chung Kuo}, Benjamin and {Yoa-Pu Hu}, Oliver and Hsiong, {Cheng Huei} and Pao, {Li Heng} and Chen, {Ting Shien} and Hung, {Chi Feng}",
year = "2003",
month = "12",
day = "1",
doi = "10.1002/bdd.373",
language = "English",
volume = "24",
pages = "367--373",
journal = "Biopharmaceutics and Drug Disposition",
issn = "0142-2782",
publisher = "John Wiley and Sons Ltd",
number = "9",

}

TY - JOUR

T1 - Single-point plasma or urine dextromethorphan method for determining CYP3A activity

AU - Pei-Chung Kuo, Benjamin

AU - Yoa-Pu Hu, Oliver

AU - Hsiong, Cheng Huei

AU - Pao, Li Heng

AU - Chen, Ting Shien

AU - Hung, Chi Feng

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

KW - CYP3A activity

KW - Dextromethorphan metabolic ratio

KW - Plasma ratio

KW - Urine ratio

UR - http://www.scopus.com/inward/record.url?scp=0346656872&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346656872&partnerID=8YFLogxK

U2 - 10.1002/bdd.373

DO - 10.1002/bdd.373

M3 - Article

C2 - 14689465

AN - SCOPUS:0346656872

VL - 24

SP - 367

EP - 373

JO - Biopharmaceutics and Drug Disposition

JF - Biopharmaceutics and Drug Disposition

SN - 0142-2782

IS - 9

ER -