Factors associated with fluoxetine and norfluoxetine plasma concentrations and clinical response in Mexican patients with mental disorders
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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%25 of the patients had no medication adherence and 40%25 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. © 2021 The Authors. Pharmacology Research %26 Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley %26 Sons Ltd.
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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%25 of the patients had no medication adherence and 40%25 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. © 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
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fluoxetine; genetic factors; norfluoxetine; pharmacokinetics; plasma concentrations cytochrome P450 2C19; cytochrome P450 2D6; cytochrome P450 3A5; fluoxetine; generic drug; norfluoxetine; olanzapine; cytochrome P450; cytochrome P450 2C19; cytochrome P450 2D6; cytochrome P450 3A; fluoxetine; neuroleptic agent; norfluoxetine; olanzapine; serotonin uptake inhibitor; absorption rate constant; adult; alcohol consumption; anxiety; Article; Beck Anxiety Inventory; blood analysis; body mass; depression; diabetes mellitus; DNA extraction; drug clearance; drug interaction; drug monitoring; epilepsy; female; genetic analysis; heredity; human; hypertension; ICD-10; liquid chromatography; liquid chromatography-mass spectrometry; male; medication compliance; mental disease; Mexican; obesity; pharmacokinetic parameters; phenotype; real time polymerase chain reaction; self report; single nucleotide polymorphism; treatment response; volume of distribution; blood; depression; genetics; genotype; mental disease; metabolism; Mexico; middle aged; pharmacogenetic variant; pharmacokinetics; psychology; treatment outcome; Adult; Antipsychotic Agents; Anxiety; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Depression; Drug Interactions; Female; Fluoxetine; Genotype; Humans; Male; Medication Adherence; Mental Disorders; Mexico; Middle Aged; Olanzapine; Pharmacogenomic Variants; Pharmacokinetics; Serotonin Uptake Inhibitors; Treatment Outcome
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