PMID- 26225262
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150730
LR  - 20181113
IS  - 2163-8306 (Print)
IS  - 2163-8306 (Electronic)
IS  - 2163-8306 (Linking)
VI  - 4
IP  - 6
DP  - 2015 Jun
TI  - A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver 
      Cirrhosis Conditions.
PG  - 338-49
LID - 10.1002/psp4.39 [doi]
AB  - Liver cirrhosis is a disease characterized by the loss of functional liver mass. 
      Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret 
      and predict how the interplay among physiological changes in cirrhosis affects 
      pharmacokinetics. However, previous PBPK models under cirrhotic conditions were 
      developed for permeable cytochrome P450 substrates and do not directly apply to 
      substrates of liver transporters. This study characterizes a PBPK model for liver 
      transporter substrates in relation to the severity of liver cirrhosis. A 
      published PBPK model structure for liver transporter substrates under healthy 
      conditions and the physiological changes for cirrhosis are combined to simulate 
      pharmacokinetics of liver transporter substrates in patients with mild and 
      moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis 
      reasonably approximate observations. This analysis includes meta-analysis to 
      obtain system-dependent parameters in cirrhosis patients and a top-down approach 
      to improve understanding of the effect of cirrhosis on transporter-mediated drug 
      disposition under cirrhotic conditions.
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 - 20150601
PL  - United States
TA  - CPT Pharmacometrics Syst Pharmacol
JT  - CPT: pharmacometrics & systems pharmacology
JID - 101580011
PMC - PMC4505828
EDAT- 2015/08/01 06:00
MHDA- 2015/08/01 06:01
PMCR- 2015/06/01
CRDT- 2015/07/31 06:00
PHST- 2015/01/15 00:00 [received]
PHST- 2015/03/27 00:00 [accepted]
PHST- 2015/07/31 06:00 [entrez]
PHST- 2015/08/01 06:00 [pubmed]
PHST- 2015/08/01 06:01 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - 10.1002/psp4.39 [doi]
PST - ppublish
SO  - CPT Pharmacometrics Syst Pharmacol. 2015 Jun;4(6):338-49. doi: 10.1002/psp4.39. 
      Epub 2015 Jun 1.