PMID- 24797229
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20181211
IS  - 1099-081X (Electronic)
IS  - 0142-2782 (Linking)
VI  - 35
IP  - 6
DP  - 2014 Sep
TI  - Development of physiologically based pharmacokinetic model to evaluate the 
      relative systemic exposure to quetiapine after administration of IR and XR 
      formulations to adults, children and adolescents.
PG  - 341-52
LID - 10.1002/bdd.1899 [doi]
AB  - Quetiapine is an atypical antipsychotic drug with a high permeability, moderate 
      solubility and defined as a Biopharmaceutics Classification System class ll 
      compound. The pharmacokinetics (PK) of the quetiapine immediate-release (IR) 
      formulation has been studied in both adults and children, but the quetiapine 
      extended-release (XR) formulation has only been conducted in adults. The purpose 
      of the current study was to use physiologically based pharmacokinetic modeling 
      (PBPK) quantitatively to predict the PK of the XR formulation in children and 
      adolescents. Using a 'learn and confirm' approach, PBPK models were developed 
      employing in vitro ADME and physicochemical data, clinical PK data of quetiapine 
      IR/XR in adults and clinical PK data of quetiapine IR in children. These models 
      can predict well the effects of CYP3A4 inhibition and induction on the PK of 
      quetiapine, the PK profile of quetiapine IR in children and adults, and the PK 
      profile of quetiapine XR in adults. The AUC and Cmax ratios (children vs adults) 
      for the different age groups were in reasonable agreement with the observed 
      ratios. In addition, the PBPK model predicted that children and adolescents are 
      likely to achieve a similar exposure following administration of either the XR 
      formulation once daily or the IR formulation twice daily at similar total daily 
      doses. The results from the study can help inform dosing regimens in pediatrics 
      using the quetiapine XR formulation.
CI  - Copyright (c) 2014 John Wiley & Sons, Ltd.
FAU - Johnson, Trevor N
AU  - Johnson TN
AD  - Simcyp Ltd, Sheffield, UK.
FAU - Zhou, Diansong
AU  - Zhou D
FAU - Bui, Khanh H
AU  - Bui KH
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20140806
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Dibenzothiazepines)
RN  - 2S3PL1B6UJ (Quetiapine Fumarate)
RN  - 33CM23913M (Carbamazepine)
RN  - 90Y4QC304K (Ketoprofen)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - EC 1.14.14.55 (CYP3A4 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antipsychotic Agents/administration & dosage/blood/*pharmacokinetics
MH  - Carbamazepine/pharmacology
MH  - Child
MH  - Computer Simulation
MH  - Cytochrome P-450 CYP2C9/metabolism
MH  - Cytochrome P-450 CYP2D6/metabolism
MH  - Cytochrome P-450 CYP3A/metabolism
MH  - Delayed-Action Preparations/administration & dosage/pharmacokinetics
MH  - Dibenzothiazepines/administration & dosage/blood/*pharmacokinetics
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - Female
MH  - Humans
MH  - Ketoprofen/pharmacology
MH  - Male
MH  - Middle Aged
MH  - *Models, Biological
MH  - Quetiapine Fumarate
MH  - Tissue Distribution
MH  - Young Adult
OTO - NOTNLM
OT  - PBPK
OT  - extended-release formulation
OT  - quetiapine
EDAT- 2014/05/07 06:00
MHDA- 2015/05/15 06:00
CRDT- 2014/05/07 06:00
PHST- 2014/02/05 00:00 [received]
PHST- 2014/04/08 00:00 [revised]
PHST- 2014/04/23 00:00 [accepted]
PHST- 2014/05/07 06:00 [entrez]
PHST- 2014/05/07 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
AID - 10.1002/bdd.1899 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2014 Sep;35(6):341-52. doi: 10.1002/bdd.1899. Epub 2014 Aug 
      6.