Factors associated with fluoxetine and norfluoxetine plasma concentrations and clinical response in Mexican patients with mental disorders

• Published in: Pharmacology research & perspectives 2021-10, Vol.9 (5), p.e00864-n/a
• Main Authors: Sagahón‐Azúa, Julia, Medellín‐Garibay, Susanna Edith, Chávez‐Castillo, Cinthya Eloisa, González‐Salinas, César Guillermo, Milán‐Segovia, Rosa del Carmen, Romano‐Moreno, Silvia
• Format: Article
• Language: English
• Subjects: Adult; Antidepressants; Antipsychotic Agents - adverse effects; Anxiety; Anxiety - drug therapy; Anxiety - psychology; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C19 - metabolism; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Cytochrome P-450 CYP3A - genetics; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Depression - drug therapy; Depression - psychology; Drug dosages; Drug Interactions; Female; fluoxetine; Fluoxetine - analogs & derivatives; Fluoxetine - blood; Fluoxetine - metabolism; Fluoxetine - pharmacokinetics; genetic factors; Genotype; Humans; Male; Mass spectrometry; Medication Adherence; Mental depression; Mental disorders; Mental Disorders - drug therapy; Mental Disorders - psychology; Mexico; Middle Aged; norfluoxetine; Olanzapine - adverse effects; Original; Pharmacogenomic Variants; Pharmacokinetics; Pharmacology; Plasma; plasma concentrations; Polymorphism; Scientific imaging; Selective Serotonin Reuptake Inhibitors - metabolism; Selective Serotonin Reuptake Inhibitors - pharmacokinetics; Serotonin; Software; Treatment Outcome
• ISSN: 2052-1707; 2052-1707
• DOI: 10.1002/prp2.864

Over the last few years, fluoxetine has been one of the most prescribed medications for the treatment of diverse psychiatric conditions in Mexico. Fluoxetine therapeutic effect is consequence of the joint action of the parent drug and its active metabolite, norfluoxetine. However, the clinical efficacy of fluoxetine, can be affected due to diverse factors, such as drug‐drug interactions and the large interindividual variability in the pharmacokinetics of this drug. The aim of this study was to determine the factors associated with variability in plasma concentrations of fluoxetine and norfluoxetine and its association with the therapeutic response. Fluoxetine and norfluoxetine plasma concentrations were quantified by liquid chromatography in 81 Mexican patients with mental disorders; 25% of the patients had no medication adherence and 40% were below the reference range of fluoxetine plus norfluoxetine plasma concentrations. The results showed that concentrations can be affected by fluoxetine metabolism caused by CYP2D6 phenotype and the concomitant administration of olanzapine. Furthermore, CYP3A5 and CYP2C19 phenotype were associated with lower anxiety and depression control during treatment with fluoxetine. This study can be a starting point to elucidate the causes of fluoxetine variable response in Mexican patients with mental disorders, as well as to detect and support medication adherence. Factors associated with fluoxetine and norfluoxetine plasma concentrations and clinical response in Mexican patients with mental disorders “The results showed that fluoxetine and norfluoxetine concentrations can be affected by fluoxetine metabolism caused by CYP2D6 phenotype and the concomitant administration of olanzapine. Furthermore, CYP3A5 and CYP2C19 phenotype were associated with lower anxiety and depression control during treatment with fluoxetine” The figure shows the box plots, in which a significant difference was found in a) concentration of fluoxetine and b) Ratio norfluoxetine/fluoxetine, between groups of CYP2D6 phenotype.