PMID- 25494035
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 2163-8306 (Print)
IS  - 2163-8306 (Electronic)
IS  - 2163-8306 (Linking)
VI  - 3
IP  - 12
DP  - 2014 Dec 10
TI  - Toward Prospective Prediction of Pharmacokinetics in OATP1B1 Genetic Variant 
      Populations.
PG  - e151
LID - 10.1038/psp.2014.50 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) models are increasingly being used 
      to provide human pharmacokinetic (PK) predictions for organic anion-transporting 
      polypeptide (OATP) substrates based on in vitro assay data. As a natural 
      extension in the application of these models, in this study, we incorporated in 
      vitro information of three major OATP1B1 genetic variants into a previously 
      reported PBPK model to predict the impact of OATP1B1 polymorphisms on human PK. 
      Using pravastatin and rosuvastatin as examples, we showed that the predicted 
      plasma concentration-time profiles in groups carrying different OATP1B1 genetic 
      variants reasonably matched the clinical observations from multiple studies. This 
      modeling and simulation approach may aid decision making in early pharmaceutical 
      research and development as well as patient-specific dose adjustment in clinical 
      practice.
FAU - Li, R
AU  - Li R
AD  - Systems Modeling and Simulation, Department of Pharmacokinetics, Dynamics, and 
      Metabolism, Pfizer Worldwide R&D, Cambridge, Massachusetts, USA.
FAU - Barton, H A
AU  - Barton HA
AD  - Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Worldwide R&D, 
      Groton, Connecticut, USA.
FAU - Maurer, T S
AU  - Maurer TS
AD  - Systems Modeling and Simulation, Department of Pharmacokinetics, Dynamics, and 
      Metabolism, Pfizer Worldwide R&D, Cambridge, Massachusetts, USA.
LA  - eng
PT  - Journal Article
DEP - 20141210
PL  - United States
TA  - CPT Pharmacometrics Syst Pharmacol
JT  - CPT: pharmacometrics & systems pharmacology
JID - 101580011
PMC - PMC4288003
EDAT- 2014/12/11 06:00
MHDA- 2014/12/11 06:00
PMCR- 2014/12/01
CRDT- 2014/12/11 06:00
PHST- 2014/05/02 00:00 [received]
PHST- 2014/09/25 00:00 [accepted]
PHST- 2014/12/11 06:00 [entrez]
PHST- 2014/12/11 06:00 [pubmed]
PHST- 2014/12/11 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - psp201450 [pii]
AID - 10.1038/psp.2014.50 [doi]
PST - epublish
SO  - CPT Pharmacometrics Syst Pharmacol. 2014 Dec 10;3(12):e151. doi: 
      10.1038/psp.2014.50.