RESUMO
The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 µM*h in EM2s to 5.8 ± 1.7 µM*h, 16.3 ± 2.9 µM*h, and 50.2 ± 7.3 µM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication.
Assuntos
Inibidores da Captação Adrenérgica/farmacocinética , Cloridrato de Atomoxetina/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Citocromo P-450 CYP2D6/genética , Adolescente , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/uso terapêutico , Alelos , Área Sob a Curva , Cloridrato de Atomoxetina/administração & dosagem , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Biotransformação , Criança , Estudos de Coortes , Citocromo P-450 CYP2C19/genética , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Medicina de PrecisãoRESUMO
OBJECTIVE: To review evidence-based literature regarding the necessary duration of antipsychotic relapse prevention in schizophrenia and related psychoses. METHOD: A computerized search was performed on Medline, Embase Psychiatry and PsycLIT which covered the period 1974-99. We also used cross-references. RESULTS: Although schizophrenia refers mainly to an intrinsic biological vulnerability, only maintenance studies with a follow-up of 2 years at most are available. Relapses appear unpredictable and occur even after long-term successful remission during antipsychotic treatment. CONCLUSION: Since rehabilitation efforts have effects only after long-term endeavours, antipsychotic relapse prevention should be maintained for long periods. It is reasonable to treat patients suffering from schizophrenia and related psychoses for longer periods than indicated by the current guidelines.
