RESUMEN
The suitability of the capillary dried blood spot (DBS) sampling method was assessed for simultaneous phenotyping of cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) using a cocktail approach. Ten volunteers received an oral cocktail capsule containing low doses of the probes bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions. They received the cocktail alone (session 1), and with the CYP inhibitors fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4, subjects received the cocktail after a 7-day pretreatment with the inducer rifampicin. The concentrations of probes/metabolites were determined in DBS and plasma using a single liquid chromatography-tandem mass spectrometry method. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. Important modulation of CYP and P-gp activities was observed in the presence of inhibitors and the inducer. Minimally invasive one- and three-point (at 2, 3, and 6 h) DBS-sampling methods were found to reliably reflect CYP and P-gp activities at each session.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/sangre , Sistema Enzimático del Citocromo P-450/sangre , Pruebas con Sangre Seca , Preparaciones Farmacéuticas/sangre , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Administración Oral , Adulto , Bupropión/administración & dosificación , Bupropión/sangre , Bupropión/farmacocinética , Cafeína/administración & dosificación , Cafeína/sangre , Cafeína/farmacocinética , Cápsulas , Bebidas Gaseosas , Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Café , Inhibidores Enzimáticos del Citocromo P-450 , Dextrometorfano/administración & dosificación , Dextrometorfano/sangre , Dextrometorfano/farmacocinética , Inhibidores Enzimáticos/administración & dosificación , Estudios de Factibilidad , Flurbiprofeno/administración & dosificación , Flurbiprofeno/sangre , Flurbiprofeno/farmacocinética , Humanos , Isoenzimas , Masculino , Midazolam/administración & dosificación , Midazolam/sangre , Midazolam/farmacocinética , Omeprazol/administración & dosificación , Omeprazol/sangre , Omeprazol/farmacocinética , Preparaciones Farmacéuticas/administración & dosificación , Fenotipo , Proyectos Piloto , Valor Predictivo de las Pruebas , Espectrometría de Masa por Ionización de Electrospray , Especificidad por Sustrato , Espectrometría de Masas en Tándem , Terfenadina/administración & dosificación , Terfenadina/análogos & derivados , Terfenadina/sangre , Terfenadina/farmacocinética , Adulto JovenRESUMEN
Forty-nine opiate-dependent persons entering remand prison were treated with methadone over 5-10 days in decreasing doses according to standard practice of the prison medical service. The prisoners were mainly young, unmarried men with an average of 5 years regular opiate use and an average of four previous imprisonments; 45% were known to be HIV infected, although routine testing was not carried out. Ten were on methadone maintenance prior to imprisonment. Urine analysis on entry detected an average of three psychoactive substances, principally opiates, benzodiazepines and cannabis. Prescribed starting doses of methadone were not correlated to independently assessed withdrawal severity. Starting doses were related to prisoners' requests and to their age. Withdrawal severity decreased after 4 days treatment but symptom relief was incomplete. Treating withdrawal symptoms on entry to prison poses unsolved ethical and practical problems.