PMID- 28971365
OWN - NLM
STAT- MEDLINE
DCOM- 20180712
LR  - 20181113
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 19
IP  - 6
DP  - 2017 Nov
TI  - Investigating Oral Absorption of Carbamazepine in Pediatric Populations.
PG  - 1864-1877
LID - 10.1208/s12248-017-0149-6 [doi]
AB  - Prediction of the pharmacokinetics of orally administered drugs in children is of 
      importance to optimize the efficacy and safety of pediatric medicines. 
      Physiologically based pharmacokinetic (PBPK) models can be helpful for this 
      purpose. However, application of these tools is limited by significant knowledge 
      gaps regarding the physiological and anatomical changes which occur with age. 
      This study aimed at investigating the age-dependent differences in oral 
      absorption of a poorly soluble model compound, carbamazepine (CBZ) in children, 
      infants, and neonates. We developed an oral absorption model in GastroPlus((R)) 
      and, after evaluation of the PBPK model for adults, extrapolation to younger ages 
      was verified with clinical data and sensitivity analyses were applied for 
      uncertain model parameters. We found that age-based scaling of physiological 
      parameters, with clearance in particular, was important to obtain adequate 
      simulation results. The sensitivity analysis revealed that CBZ absorption was 
      influenced by solubility, particle radius, and small intestinal transit time 
      depending on the pediatric age group and CBZ dose. However, in vitro dissolution 
      testing using proposed pediatric biorelevant media suggested no major age 
      dependency of dissolution kinetics. Such better understanding of oral absorption 
      in pediatric patients is required to improve the prediction of exposure in 
      children and the confidence in oral biopharmaceutical tools.
FAU - Kohlmann, Philip
AU  - Kohlmann P
AD  - Formulation Research & Development, F. Hoffmann-La Roche Ltd., Basel, 
      Switzerland.
FAU - Stillhart, Cordula
AU  - Stillhart C
AD  - Formulation Research & Development, F. Hoffmann-La Roche Ltd., Basel, 
      Switzerland.
FAU - Kuentz, Martin
AU  - Kuentz M
AD  - Institute of Pharmaceutical Technology, University of Applied Sciences and Arts 
      Northwestern Switzerland, Muttenz, Switzerland.
FAU - Parrott, Neil
AU  - Parrott N
AD  - Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche 
      Innovation Center Basel, Grenzacherstrasse 124, 4070, Basel, Switzerland. 
      neil_john.parrott@roche.com.
LA  - eng
PT  - Journal Article
DEP - 20171002
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 33CM23913M (Carbamazepine)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Carbamazepine/chemistry/*pharmacokinetics
MH  - Child
MH  - Child, Preschool
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - *Intestinal Absorption
MH  - Models, Biological
MH  - Solubility
OTO - NOTNLM
OT  - BCS2
OT  - PBPK modeling
OT  - in vitro dissolution
OT  - oral absorption
OT  - pediatric biopharmaceutics
EDAT- 2017/10/04 06:00
MHDA- 2018/07/13 06:00
CRDT- 2017/10/04 06:00
PHST- 2017/06/24 00:00 [received]
PHST- 2017/09/14 00:00 [accepted]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2018/07/13 06:00 [medline]
PHST- 2017/10/04 06:00 [entrez]
AID - 10.1208/s12248-017-0149-6 [pii]
AID - 10.1208/s12248-017-0149-6 [doi]
PST - ppublish
SO  - AAPS J. 2017 Nov;19(6):1864-1877. doi: 10.1208/s12248-017-0149-6. Epub 2017 Oct 
      2.