RESUMEN
A new HPLC assay was developed to study dextromethorphan O-demethylation to dextrorphan in vitro using human liver microsomes to investigate the activity of the polymorphic monooxygenase cytochrome P450 2D6 (CYP 2D6). The separation of dextromethorphan and its main metabolite dextrorphan was performed on a polymeric C18 reversed-phase column with UV-detection using levallorphan as an internal standard. Liver samples from ten subjects were screened for dextrorphan formation whereby three groups with different abilities to metabolize dextromethorphan could be found. Seven microsomal preparations from extensive metabolizers showed an average dextrorphan formation rate of 298 +/- 68 pmol/mg protein.min, one sample was classified to belong to an intermediate dextromethorphan metabolizer (79 pmol/mg protein.min), whereas two samples of poor metabolizers exhibited significantly lower rates of dextromethorphan metabolism with values of 11 and 27 pmol/mg protein.min, respectively. This assay permits not only a fast in vitro screening for cytochrome P450 2D6 monooxygenase activity but is also an excellent tool to determine potential drug-drug interactions with this important metabolizing enzyme.
Asunto(s)
Antitusígenos/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Dextrometorfano/metabolismo , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , Adulto , Anciano , Cromatografía Líquida de Alta Presión , Citocromo P-450 CYP2D6/química , Remoción de Radical Alquila , Dextrorfano/farmacocinética , Antagonistas de Aminoácidos Excitadores/farmacocinética , Femenino , Humanos , Técnicas In Vitro , Masculino , Microsomas Hepáticos/efectos de los fármacos , Persona de Mediana Edad , Espectrofotometría UltravioletaRESUMEN
In a retrospective study 62 patients, who fulfilled the ICD-8/9 criteria for obsessive-compulsive disorder (OCD), were followed up. Besides an assessment of the cross-sectional symptomatology of OCD and depression, the long-term course of OCD and its relationship to depression were investigated. Five courses of OCD could be differentiated: continuous and unchanging (27.4%); continuous with deterioration (9.7%); continuous with improvement (24.4%); episodic with partial remission (24.2%), and episodic with full remission (11.3%). There was no difference between primary or secondary depression on the prognosis of OCD, and there was also no difference between the continuous or episodic course with regard to primary or secondary depression. Our results may be biased by the fact that we selected a sample of OCD and not primarily major depressive patients.