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1.
Br J Clin Pharmacol ; 84(8): 1738-1747, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29618168

RESUMO

AIMS: To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11-18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. METHODS: Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20-h urine samples were collected per participant. RESULTS: Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0-∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. CONCLUSION: Oral clearance of CLZ was increased two-fold in obese children vs. nonobese children aged 11-18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ.


Assuntos
Clorzoxazona/farmacocinética , Citocromo P-450 CYP2E1/metabolismo , Obesidade/metabolismo , Administração Oral , Adolescente , Área Sob a Curva , Índice de Massa Corporal , Criança , Clorzoxazona/administração & dosagem , Diabetes Mellitus , Relação Dose-Resposta a Droga , Fígado Gorduroso , Feminino , Humanos , Hidroxilação , Masculino , Taxa de Depuração Metabólica/fisiologia , Obesidade/sangue , Obesidade/fisiopatologia , Obesidade/urina
2.
J Chromatogr A ; 867(1-2): 219-33, 2000 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-10670723

RESUMO

The control on use of anabolic agents in meat producing animals is generally based on urine, faeces or hair analysis. This exercise, which is usually performed in slaughterhouses or on farms, is not relevant to imported carcasses or retail meat. A single sensitive method for a wide range of anabolic steroids was developed. After extraction of the lyophilised meat, enzymatic hydrolysis was used for deconjugation. Solid-phase extraction on a polymeric stationary phase was performed prior to hydrolysis of ester residues under alkaline conditions. Liquid-liquid partitioning was used to separate the analytes into two main categories: phenol containing molecules, such as phenolic steroids, resorcylic acid lactones and stilbenes, and delta4-3-one containing molecules, such as most androgens and progestagens. Solid-phase extraction on silica columns was performed before applying a specific derivatisation for each compound sub-group. The combination of high-resolution chromatography with a quadrupole mass spectrometer permitted detection of 23 steroids in the 5-100 ng/kg range. Ion chromatograms for residue positive samples are shown and discussed.


Assuntos
Anabolizantes/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Carne/análise , Cromatografia Líquida , Ésteres , Hidrólise , Fenóis/isolamento & purificação , Sensibilidade e Especificidade
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