Risperidone and Venlafaxine Metabolic Ratios Strongly Predict a CYP2D6 Poor Metabolizing Genotype.

Abstract

PURPOSE:

To investigate the predictive value of the risperidone and venlafaxine metabolic ratios and CYP2D6 genotype.

METHODS:

The determination of risperidone, 9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N-desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients, respectively. The receiver operator characteristic method and the area under the receiver operator characteristic curve were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. To evaluate the proposed cutoff levels of >1 to identify individuals with a poor CYP2D6 genotype, the sensitivity, specificity, positive predictive values, and negative predictive values were calculated.

RESULTS:

Area under the receiver operator characteristic curve to predict poor metabolizers for risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine ratios was 93% and 99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value (confidence interval) of a risperidone/9-hydroxyrisperidone ratio >1 to predict a CYP2D6 poor metabolizer genotype were 91% (76%-97%), 86% (83%-89%), 35% (26%-46%), and 99% (97%-100%), respectively. The corresponding measures for N-desmethylvenlafaxine/O-desmethylvenlafaxine were 93% (76%-97%), 87% (83%-89%), 40% (32%-51%), and 99% (98%-100%).

CONCLUSIONS:

Risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine metabolic ratios >1 strongly predict individuals with poor metabolizer genotype, which could guide psychotropic drug treatment to avoid adverse drug reactions and to increase their therapeutic efficacy in patients prescribed these drugs.

• Authors: Buster Mannheimer, Tore Haslemo, Jonatan D Lindh, Erik Eliasson, Espen Molden
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 38 Issue 1 Pg. 127-34 (Feb 2016) ISSN: 1536-3694 [Electronic] United States
• PMID: 26418700 (Publication Type: Journal Article, Validation Study)

Chemical References

• Antidepressive Agents, Second-Generation
• Antipsychotic Agents
• Cyclohexanols
• N-desmethylvenlafaxine
• Venlafaxine Hydrochloride
• Cytochrome P-450 CYP2D6
• Risperidone
• Paliperidone Palmitate
• Desvenlafaxine Succinate

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antidepressive Agents, Second-Generation (pharmacokinetics)
• Antipsychotic Agents (pharmacokinetics)
• Child
• Cyclohexanols (pharmacokinetics)
• Cytochrome P-450 CYP2D6 (genetics)
• Desvenlafaxine Succinate (pharmacokinetics)
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Paliperidone Palmitate (pharmacokinetics)
• Predictive Value of Tests
• Retrospective Studies
• Risperidone (pharmacokinetics)
• Sensitivity and Specificity
• Venlafaxine Hydrochloride (pharmacokinetics)
• Young Adult