PMID- 23269526
OWN - NLM
STAT- MEDLINE
DCOM- 20131022
LR  - 20211021
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 15
IP  - 2
DP  - 2013 Apr
TI  - Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.
PG  - 377-87
LID - 10.1208/s12248-012-9446-2 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) models are built using differential 
      equations to describe the physiology/anatomy of different biological systems. 
      Readily available in vitro and in vivo preclinical data can be incorporated into 
      these models to not only estimate pharmacokinetic (PK) parameters and plasma 
      concentration-time profiles, but also to gain mechanistic insight into compound 
      properties. They provide a mechanistic framework to understand and extrapolate PK 
      and dose across in vitro and in vivo systems and across different species, 
      populations and disease states. Using small molecule and large molecule examples 
      from the literature and our own company, we have shown how PBPK techniques can be 
      utilised for human PK and dose prediction. Such approaches have the potential to 
      increase efficiency, reduce the need for animal studies, replace clinical trials 
      and increase PK understanding. Given the mechanistic nature of these models, the 
      future use of PBPK modelling in drug discovery and development is promising, 
      however some limitations need to be addressed to realise its application and 
      utility more broadly.
FAU - Jones, Hannah M
AU  - Jones HM
AD  - Systems Modelling and Simulation Group, Department of Pharmacokinetics, Dynamics 
      and Metabolism, Pfizer Worldwide R&D, 35 Cambridgepark Drive, Cambridge, MA 
      02140, USA. Hannah.Jones@pfizer.com
FAU - Mayawala, Kapil
AU  - Mayawala K
FAU - Poulin, Patrick
AU  - Poulin P
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20121227
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Drug Administration Routes
MH  - Drug Discovery/*methods
MH  - *Drug Dosage Calculations
MH  - Humans
MH  - Intestinal Absorption
MH  - Metabolic Clearance Rate
MH  - *Models, Biological
MH  - Pharmaceutical Preparations/*administration & dosage/*metabolism
MH  - *Pharmacokinetics
MH  - Reproducibility of Results
MH  - Species Specificity
MH  - Tissue Distribution
PMC - PMC3675752
EDAT- 2012/12/28 06:00
MHDA- 2013/10/23 06:00
PMCR- 2013/12/27
CRDT- 2012/12/28 06:00
PHST- 2012/06/04 00:00 [received]
PHST- 2012/11/28 00:00 [accepted]
PHST- 2012/12/28 06:00 [entrez]
PHST- 2012/12/28 06:00 [pubmed]
PHST- 2013/10/23 06:00 [medline]
PHST- 2013/12/27 00:00 [pmc-release]
AID - 9446 [pii]
AID - 10.1208/s12248-012-9446-2 [doi]
PST - ppublish
SO  - AAPS J. 2013 Apr;15(2):377-87. doi: 10.1208/s12248-012-9446-2. Epub 2012 Dec 27.