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Open‐label steady‐state pharmacokinetic drug interaction study on co‐administered quetiapine fumarate and divalproex sodium in patients with schizophrenia, schizoaffective disorder, or bipolar disorder
Author(s) -
Winter Helen R.,
DeVane C. Lindsay,
Figueroa Carlos,
Ennis Debra J.,
HamerMaansson Jennifer E.,
Davis Patty C.,
Smith Mark A.
Publication year - 2007
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.869
Subject(s) - quetiapine , divalproex , bipolar disorder , schizoaffective disorder , quetiapine fumarate , pharmacokinetics , tolerability , bipolar i disorder , cohort , valproic acid , area under the curve , medicine , pharmacology , atypical antipsychotic , psychiatry , schizophrenia (object oriented programming) , adverse effect , mania , psychosis , lithium (medication) , antipsychotic , epilepsy
Objective To determine whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium. Methods The pharmacokinetics and short‐term tolerability and safety of coadministered quetiapine and divalproex were examined in adults with schizophrenia/schizoaffective disorder (Cohort A) or bipolar disorder (Cohort B) in an open‐label, parallel, 2‐cohort drug‐interaction study conducted at three centers in the United States. Cohort A was administered quetiapine (150 mg bid) prospectively for 13 days, with divalproex (500 mg bid) added on days 6–13. Cohort B was administered divalproex (500 mg bid) for 16 days, with quetiapine (150 mg bid) added on days 9–16. Quetiapine and valproic acid plasma concentration–time data over a 12‐h steady‐state dosing interval were used to determine C max , T max , C min , area under the plasma concentration–time curve (AUC τ ), and oral clearance (CL/F). Results In Cohort A ( n = 18), addition of divalproex did increase the C max of quetiapine by 17% but did not change AUC τ . In Cohort B ( n = 15), addition of quetiapine decreased both total valproic acid C max and AUC τ by 11%. No differences were observed in adverse events (AEs) with either quetiapine or divalproex monotherapy or their combination. Conclusion Combination therapy with quetiapine (150 mg bid) and divalproex (500 mg bid) resulted in small and statistically non‐significant pharmacokinetic changes. Copyright © 2007 John Wiley & Sons, Ltd.