J 2012

Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice

JUŘICA, Jan, Richard BARTEČEK, Alexandra ŽOURKOVÁ, Eva PINDUROVÁ, Alexandra ŠULCOVÁ et. al.

Basic information

Original name

Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice

Authors

JUŘICA, Jan (203 Czech Republic, belonging to the institution), Richard BARTEČEK (203 Czech Republic, belonging to the institution), Alexandra ŽOURKOVÁ (203 Czech Republic, belonging to the institution), Eva PINDUROVÁ (203 Czech Republic, belonging to the institution), Alexandra ŠULCOVÁ (203 Czech Republic, guarantor, belonging to the institution), Tomáš KAŠPÁREK (203 Czech Republic, belonging to the institution) and Ondřej ZENDULKA (203 Czech Republic, belonging to the institution)

Edition

JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS, HOBOKEN, WILEY-BLACKWELL, 2012, 0269-4727

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 2.104

RIV identification code

RIV/00216224:14740/12:00060574

Organization unit

Central European Institute of Technology

UT WoS

000305894800020

Keywords in English

CYP2D6; dextromethorphan; genotype; metabolic ratio; phenotype; serum

Tags

Tags

International impact, Reviewed
Změněno: 8/4/2013 11:02, Olga Křížová

Abstract

V originále

What is known and Objective: Accurate prediction of actual CYP2D6 metabolic activity may prevent some adverse drug reactions and improve therapeutic response in patients receiving CYP2D6 substrates. Dextromethorphan-to-dextrorphan metabolic ratio (MRDEM/DOR) is well established as a marker of CYP2D6 metabolizer status. The relationship between urine and plasma or serum MRDEM/DOR is not well established nor is there evidence of antimode for separation of intermediate and especially poor metabolizers (PM) from extensive metabolizers (EM). This study addressed whether CYP2D6 phenotyping using molar metabolic ratio of dextromethorphan to dextrorphan (MRDEM/DOR) in serum is usable and reliable in clinical practice as urinary MRDEM/DOR. Methods: We measured MRDEM/DOR in serum and CYP2D6 genotype in 51 drug-naive patients and 30 volunteers. Receiver-operator characteristic (ROC) analysis was used for the evaluation of optimum cut-off value for discriminating between extensive, intermediate and PM. In addition, we studied the correlation of serum MRDEM/DOR with urine MRDEM/DOR in the 30 healthy volunteers. Results and Discussion: A trimodal distribution of log MRDEM/DOR in serum was observed, with substantial overlap between extensive and intermediate metabolizer groups. We obtained an acceptable cut-off serum MRDEM/DOR value to discriminate between PM and either extensive or extensive + intermediate metabolizers. Using serum MRDEM/DOR, it seems to be unreliable to discriminate EM from intermediate metabolizers (IM). A strong correlation between serum MRDEM/DOR and urine MRDEM/DOR was found. What is new and Conclusion: Serum MRDEM/DOR (3 h) correlated with MRDEM/DOR in urine (08 h). Serum MRDEM/DOR discriminated between extensive and PM and between extensive + intermediate and PM. Our CYP2D6 phenotyping using serum dextromethorphan/dextrorphan molar ratio appears reliable but requires independent validation.

Links

ED1.1.00/02.0068, research and development project
Name: CEITEC - central european institute of technology
NS9676, research and development project
Name: Vliv farmakogenetických a farmakokinetických faktorů na účinnost a bezpečnost terapie prvních epizod schizofrenie
Investor: Ministry of Health of the CR