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- W2388524749 abstract "OBJECTIVE To study the metabolic mechanism of quetiapine at clinical therapeutic dose.METHODS Nineteen patients received multiple doses of quetiapine(200 mg,twice daily) with or without concomitant erythromycin(500 mg,three times daily).At the same time,midazolam was given to detect the enzyme activity.Blood samples were collected at specified time intervals.Concentrations of quetiapine and some metabolites in plasma were assayed by HPLC-MS/ESI+,as well as midazolam and its metabolite by HPLC-UV.RESULTS In the presence of erythromycin,the activity of CYP3A4 decreased significantly.For quetiapine,the ρSSmax,AUCSS0-24 and t1/2 elevated significantly,the ratio of CL/F decreased significantly,the variation of AUCSS0-24 and CL/F was significantly negative and positive correlated to that of CYP3A4 activity respectively.For quetiapine sulfoxide,the ρSSmax and AUCSS0-24 decreased significantly,the t1/2 elevated significantly,and the variation of t1/2 was significantly positive correlated to that of CYP3A4 activity.For 7-hydroxy-quetiapine,the ρSSmax and AUCSS0-24 showed no statistical change,the t1/2 elevated significantly and was closely correlated to CYP3A4 activity.For 7-hydroxy-N-desalkyl-quetiapine,the t1/2 showed no statistical change,the ρSSmax and AUCSS0-24 decreased significantly,and the variation of AUCSS0-24 was significantly positive correlated to that of CYP3A4 activity.CONCLUSION The major metabolic pathway of quetiapine is sulfoxidation.CYP3A4 is the primary enzyme responsible for the CYP-mediated metabolism of quetiapine at clinical therapy dosage in vivo.Quetiapine sulfoxidation and N-dealkylation are mainly catalyzed by CYP3A4.7-Hydroxylation of quetiapine is not mainly catalyzed by CYP3A4." @default.
- W2388524749 created "2016-06-24" @default.
- W2388524749 creator A5064832836 @default.
- W2388524749 date "2007-01-01" @default.
- W2388524749 modified "2023-09-28" @default.
- W2388524749 title "Metabolic Mechanism of Quetiapine at Clinical Therapeutic Dose in Vivo" @default.
- W2388524749 hasPublicationYear "2007" @default.
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