Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity

A. Llerena, R. Berecz, A. De la Rubia, M. J. Norberto, J. Benitez

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously to elderly patients because potentially dangerous metabolic interactions may occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients to avoid drug interactions, which depend on the metabolic phenotype. The goal of this study was to evaluate the use of the mesoridazine/thioridazine ratio for the estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been developed for the determination of thioridazine and its metabolites, mesoridazine and sulforidazine. Commonly used central nervous system (CNS) comedications do not interfere with the method. A group of 27 chronic patients with mental illness receiving monotherapy with thioridazine were studied. There were 23 men and 4 women between 37 and 80 years old (mean ±SD: 61.2 ± 10.2). The thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio (r = 0.74, p <0.001). Therefore, the authors suggest that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment.

Original languageEnglish
Pages (from-to)397-401
Number of pages5
JournalTherapeutic Drug Monitoring
Volume22
Issue number4
DOIs
Publication statusPublished - 2000

Fingerprint

Mesoridazine
Thioridazine
Cytochrome P-450 CYP2D6
Enzyme activity
Enzymes
Metabolites
Debrisoquin
Drug interactions
Mentally Ill Persons
Neurology
Drug Interactions
Central Nervous System
Phenotype
Substrates

Keywords

  • CYP2D6
  • High-pressure liquid chromatography
  • Pharmacogenetics
  • Therapeutic drug monitoring (TDM)
  • Thioridazine

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis
  • Pharmacology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health

Cite this

Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity. / Llerena, A.; Berecz, R.; De la Rubia, A.; Norberto, M. J.; Benitez, J.

In: Therapeutic Drug Monitoring, Vol. 22, No. 4, 2000, p. 397-401.

Research output: Contribution to journalArticle

Llerena, A. ; Berecz, R. ; De la Rubia, A. ; Norberto, M. J. ; Benitez, J. / Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity. In: Therapeutic Drug Monitoring. 2000 ; Vol. 22, No. 4. pp. 397-401.
@article{c1644be5869e401fac76c06a7347d030,
title = "Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity",
abstract = "Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously to elderly patients because potentially dangerous metabolic interactions may occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients to avoid drug interactions, which depend on the metabolic phenotype. The goal of this study was to evaluate the use of the mesoridazine/thioridazine ratio for the estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been developed for the determination of thioridazine and its metabolites, mesoridazine and sulforidazine. Commonly used central nervous system (CNS) comedications do not interfere with the method. A group of 27 chronic patients with mental illness receiving monotherapy with thioridazine were studied. There were 23 men and 4 women between 37 and 80 years old (mean ±SD: 61.2 ± 10.2). The thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio (r = 0.74, p <0.001). Therefore, the authors suggest that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment.",
keywords = "CYP2D6, High-pressure liquid chromatography, Pharmacogenetics, Therapeutic drug monitoring (TDM), Thioridazine",
author = "A. Llerena and R. Berecz and {De la Rubia}, A. and Norberto, {M. J.} and J. Benitez",
year = "2000",
doi = "10.1097/00007691-200008000-00006",
language = "English",
volume = "22",
pages = "397--401",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity

AU - Llerena, A.

AU - Berecz, R.

AU - De la Rubia, A.

AU - Norberto, M. J.

AU - Benitez, J.

PY - 2000

Y1 - 2000

N2 - Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously to elderly patients because potentially dangerous metabolic interactions may occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients to avoid drug interactions, which depend on the metabolic phenotype. The goal of this study was to evaluate the use of the mesoridazine/thioridazine ratio for the estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been developed for the determination of thioridazine and its metabolites, mesoridazine and sulforidazine. Commonly used central nervous system (CNS) comedications do not interfere with the method. A group of 27 chronic patients with mental illness receiving monotherapy with thioridazine were studied. There were 23 men and 4 women between 37 and 80 years old (mean ±SD: 61.2 ± 10.2). The thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio (r = 0.74, p <0.001). Therefore, the authors suggest that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment.

AB - Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously to elderly patients because potentially dangerous metabolic interactions may occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients to avoid drug interactions, which depend on the metabolic phenotype. The goal of this study was to evaluate the use of the mesoridazine/thioridazine ratio for the estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been developed for the determination of thioridazine and its metabolites, mesoridazine and sulforidazine. Commonly used central nervous system (CNS) comedications do not interfere with the method. A group of 27 chronic patients with mental illness receiving monotherapy with thioridazine were studied. There were 23 men and 4 women between 37 and 80 years old (mean ±SD: 61.2 ± 10.2). The thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio (r = 0.74, p <0.001). Therefore, the authors suggest that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment.

KW - CYP2D6

KW - High-pressure liquid chromatography

KW - Pharmacogenetics

KW - Therapeutic drug monitoring (TDM)

KW - Thioridazine

UR - http://www.scopus.com/inward/record.url?scp=0033860864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033860864&partnerID=8YFLogxK

U2 - 10.1097/00007691-200008000-00006

DO - 10.1097/00007691-200008000-00006

M3 - Article

C2 - 10942178

AN - SCOPUS:0033860864

VL - 22

SP - 397

EP - 401

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 4

ER -