PMID- 17729385
OWN - NLM
STAT- MEDLINE
DCOM- 20080117
LR  - 20151119
IS  - 0885-6222 (Print)
IS  - 0885-6222 (Linking)
VI  - 22
IP  - 7
DP  - 2007 Oct
TI  - 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.
PG  - 469-76
AB  - 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(tau)), 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(tau). In Cohort B (n = 15), addition of 
      quetiapine decreased both total valproic acid C(max) and AUC(tau) 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.
CI  - Copyright 2007 John Wiley & Sons, Ltd.
FAU - Winter, Helen R
AU  - Winter HR
AD  - AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA. helen.winter@astrazeneca.com
FAU - DeVane, C Lindsay
AU  - DeVane CL
FAU - Figueroa, Carlos
AU  - Figueroa C
FAU - Ennis, Debra J
AU  - Ennis DJ
FAU - Hamer-Maansson, Jennifer E
AU  - Hamer-Maansson JE
FAU - Davis, Patty C
AU  - Davis PC
FAU - Smith, Mark A
AU  - Smith MA
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Psychopharmacol
JT  - Human psychopharmacology
JID - 8702539
RN  - 0 (Antimanic Agents)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Dibenzothiazepines)
RN  - 2S3PL1B6UJ (Quetiapine Fumarate)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Adult
MH  - Antimanic Agents/adverse effects/*pharmacokinetics/pharmacology
MH  - Antipsychotic Agents/adverse effects/*pharmacokinetics/pharmacology
MH  - Area Under Curve
MH  - Bipolar Disorder/*drug therapy
MH  - Cohort Studies
MH  - Dibenzothiazepines/adverse effects/*pharmacokinetics/pharmacology
MH  - Drug Interactions
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Quetiapine Fumarate
MH  - Schizophrenia/*drug therapy
MH  - Schizophrenic Psychology
MH  - United States
MH  - Valproic Acid/adverse effects/*pharmacokinetics/pharmacology
EDAT- 2007/08/31 09:00
MHDA- 2008/01/18 09:00
CRDT- 2007/08/31 09:00
PHST- 2007/08/31 09:00 [pubmed]
PHST- 2008/01/18 09:00 [medline]
PHST- 2007/08/31 09:00 [entrez]
AID - 10.1002/hup.869 [doi]
PST - ppublish
SO  - Hum Psychopharmacol. 2007 Oct;22(7):469-76. doi: 10.1002/hup.869.