ABSTRACT
Objetivo: mensurar a prevalência da coprescrição de psicofármacos inibidores clinicamente significativos da enzima CYP2D6. Métodos: estudo transversal realizado com usuários do Centro de Atenção Psicossocial de um município da Amazônia Legal. Os dados foram coletados de prontuário (medicamentos e diagnóstico clínico) e questionário semiestruturado (sociodemográficos). As informações referentes às medicações (substrato/inibidor da CYP2D6) foram consultadas no Micromedex®, Drug Interaction Checker, Food and Drug Administration e The Pharmacogene Variation Consortium. Os dados foram interpretados utilizando estatística descritiva percentual simples, considerando a média e o desvio-padrão. Para a confecção do banco de dados, utilizou-se o Office Excel®2010. Estudo aprovado pelo Comitê de Ética em Pesquisa sob o Parecer nº 289.937. Resultados: participaram deste estudo 43 pessoas com média de idade de 40,98 (±11,04) anos, sendo 55,81% do sexo masculino, 81,39% solteiros, 88,37% não brancos (pretos/pardos), 58,14% estudaram até o ensino médio e 62,79% tiveram diagnóstico F20 (esquizofrenia e subdivisões). Entre a população estudada, 100% (43/43) faziam uso diário de haloperidol, e 95,34% (41/43) encontravam-se em uso rotineiro de mais de uma droga metabolizada pela enzima CYP2D6. Verificou-se que 93% (40/43) dos participantes continham coprescrição de substratos e inibidores da enzima CYP2D6, sendo a maior prevalência de prescrições envolvendo ácido valproico, clorpromazina, levomepromazina, prometazina e risperidona. Conclusão: o estudo pôde mensurar alta prevalência de coprescrição de psicofármacos inibidores clinicamente significativos da enzima CYP2D6.
Introduction: Clinically significant adverse drug reactions are seldomly frequent, but their incidence rises when there is co-prescription, especially psychoactive drugs metabolized by the enzyme CYP2D6. Objective: To measure the prevalence of co-prescription of clinically significant CYP2D6 enzyme inhibitors. Methods: Cross-sectional study conducted with users of the Center for Psychosocial Attention in a city of Legal Amazon. Sociodemographic, health and drug profile data were collected from patients' records. Possible enzymatic inductions or inhibitions were researched in Micromedex®, Drug Interaction Checker, Food and Drug Administration e The Pharmacogene Variation Consortium. The data were interpreted using simple percentage descriptive statistics, considering the mean and standard deviation. To make the database, Office Excel®2010 was used. The research has the approval of the Research Ethics Committee under opinion no. 289,937. Results: Forty-three people with a mean age of 40.98 (±11.04) years participated in this study, 24 (55.81%) men, 81,39% single, 88,37% non-white, 58,14% have high school and 62,79% were diagnosed with schizophrenia. Among the studied population, 100% (43/43) used haloperidol daily and 95.34% (41/43) used more than one drug inhibitor or metabolized by the CYP2D6 enzyme. It was found that 93% of the participants contained co-prescription of CYP2D6 substrates and inhibitors, with the highest prevalence of prescriptions involving valproic acid, chlorpromazine, levomepromazine, promethazine and risperidone. Conclusion: The study was able to measure the high prevalence of co-prescription of clinically significant CYP2D6 inhibitor drugs in the studied population.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Psychotropic Drugs/therapeutic use , Prescription Drugs/therapeutic use , Cytochrome P-450 CYP2D6 Inhibitors/therapeutic use , Mental Disorders/drug therapy , Psychotropic Drugs/adverse effects , Schizophrenia/drug therapy , Cross-Sectional Studies , Drug Interactions , Cytochrome P-450 CYP2D6 Inhibitors/adverse effectsABSTRACT
Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.
Subject(s)
Animals , Male , Rats , Berberine , Chemistry , Metabolism , Chromatography, High Pressure Liquid , Cytochrome P-450 CYP2D6 , Metabolism , Cytochrome P-450 CYP2D6 Inhibitors , Chemistry , Metabolism , Drugs, Chinese Herbal , Chemistry , Metabolism , Microsomes, Liver , Metabolism , Molecular Structure , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
The paper is aimed to study the metabolic characteristics of osthol (Ost) in isolated hepatocytes of rat to identify which isoforms of CYP450 were responsible for Ost metabolism in vitro. The concentration of Ost in isolated hepatocytes incubation system was determined by HPLC-UV. The effects of incubation time, substrate concentration and hepatocytes amount on the metabolic characteristics of Ost were investigated. CYP2C8 inhibitor quercetin (Que), CYP2C9 inhibitor sulfaphenazole (Sul), CYP2D6 inhibitor yohimbine (Yoh), CYP3A4 inhibitor troleandomycin (Tro) and CYP450 inducer rifampicin (Rif) were used to investigate their effects on the metabolism of Ost. The metabolism of Ost in isolated rat hepatocytes showed an enzymatic kinetic characteristics. Rif induced Ost elimination in rat hepatocytes; Yoh, Sul, Que did not have effects on Ost metabolism in vitro. Between 0-200 micromol x L(-1), Tro inhibited Ost metabolism in a concentration-dependent manner. CYP3A4 is the enzyme metabolizing Ost in vitro; CYP2C8, CYP2C9 and CYP2D6 did not involve in Ost metabolism in rat hepatocytes.