Journal
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
Volume 60, Issue 11, Pages 791-795Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00228-004-0853-x
Keywords
quetiapine; erythromycin; metabolism; interaction
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Objective: To study the effect of erythromycin on metabolism of quetiapine in Chinese suffering from schizophrenia. Methods: Nineteen patients received multiple doses of quetiapine (200 mg, twice daily) with or without coadministered erythromycin (500 mg, three times daily). Blood samples were collected at specified time intervals for determination of plasma concentrations of quetiapine and some of its metabolites. Results: With erythromycin co-administration: for quetiapine, maximal plasma concentration (C-max), area under concentration-time curve of 0-infinity h (AUC(0 infinity)) and terminal-phase elimination half-life time (t(1/2) increased 68, 129 and 92%, respectively, and clearance (CL) and terminal elimination rate constant (K-e) decreased 52% and 55%, respectively; for quetiapine sulfoxide (QTP-SF), C-max, AUC(0 infinity) and AUC ratio decreased 64, 23, and 70%, respectively, and t(1/2) increased 211%; for 7-hydroxy-quetiapine (QTP-H), K-e and AUC ratio decreased 61% and 45%, respectively, and t(1/2) increased 203%; for 7-hydroxy-N-desalkyl-quetiapine (QTP-ND), C-max, AUC(0-infinity) and AUC ratio decreased 36, 40 and 71%, respectively. Conclusion: Erythromycin has a noticeable effect on the metabolism of quetiapine. When quetiapine is co-administered with CYP3A inhibitors such as erythromycin, the dosing regimen should be modified according to quetiapine TDM.
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