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

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.

Základní údaje

Originální název

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

Autoři

JUŘICA, Jan (203 Česká republika, domácí), Richard BARTEČEK (203 Česká republika, domácí), Alexandra ŽOURKOVÁ (203 Česká republika, domácí), Eva PINDUROVÁ (203 Česká republika, domácí), Alexandra ŠULCOVÁ (203 Česká republika, garant, domácí), Tomáš KAŠPÁREK (203 Česká republika, domácí) a Ondřej ZENDULKA (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.104

Kód RIV

RIV/00216224:14740/12:00060574

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1111/j.1365-2710.2012.01333.x

UT WoS

000305894800020

Klíčová slova anglicky

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

Štítky

ok, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 4. 2013 11:02, Olga Křížová

Anotace

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.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

NS9676, projekt VaV

Název: Vliv farmakogenetických a farmakokinetických faktorů na účinnost a bezpečnost terapie prvních epizod schizofrenie

Investor: Ministerstvo zdravotnictví ČR, Vliv farmakogenetických a farmakokinetických faktorů na účinnost a bezpečnost terapie prvních epizod schizofrenie

Citovat

JUŘICA, Jan, Richard BARTEČEK, Alexandra ŽOURKOVÁ, Eva PINDUROVÁ, Alexandra ŠULCOVÁ, Tomáš KAŠPÁREK a Ondřej ZENDULKA. Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice. JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS. HOBOKEN: WILEY-BLACKWELL, 2012, roč. 37, č. 4, s. 486-490. ISSN 0269-4727. Dostupné z: https://dx.doi.org/10.1111/j.1365-2710.2012.01333.x.

@article{989156,
   author = {Juřica, Jan and Barteček, Richard and Žourková, Alexandra and Pindurová, Eva and Šulcová, Alexandra and Kašpárek, Tomáš and Zendulka, Ondřej},
   article_location = {HOBOKEN},
   article_number = {4},
   doi = {http://dx.doi.org/10.1111/j.1365-2710.2012.01333.x},
   keywords = {CYP2D6; dextromethorphan; genotype; metabolic ratio; phenotype; serum},
   language = {eng},
   issn = {0269-4727},
   journal = {JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS},
   title = {Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice},
   url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2012.01333.x/abstract},
   volume = {37},
   year = {2012}
}

TY  - JOUR
ID  - 989156
AU  - Juřica, Jan - Barteček, Richard - Žourková, Alexandra - Pindurová, Eva - Šulcová, Alexandra - Kašpárek, Tomáš - Zendulka, Ondřej
PY  - 2012
TI  - Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice
JF  - JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
VL  - 37
IS  - 4
SP  - 486-490
EP  - 486-490
PB  - WILEY-BLACKWELL
SN  - 02694727
KW  - CYP2D6
KW  - dextromethorphan
KW  - genotype
KW  - metabolic ratio
KW  - phenotype
KW  - serum
UR  - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2012.01333.x/abstract
L2  - http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2012.01333.x/abstract
N2  - 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.
ER  -

JUŘICA, Jan, Richard BARTEČEK, Alexandra ŽOURKOVÁ, Eva PINDUROVÁ, Alexandra ŠULCOVÁ, Tomáš KAŠPÁREK a Ondřej ZENDULKA. Serum dextromethorphan/dextrorphan metabolic ratio for CYP2D6 phenotyping in clinical practice. \textit{JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS}. HOBOKEN: WILEY-BLACKWELL, 2012, roč.~37, č.~4, s.~486-490. ISSN~0269-4727. Dostupné z: https://dx.doi.org/10.1111/j.1365-2710.2012.01333.x.

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