PMID- 25505653
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141216
LR  - 20200929
IS  - 2193-9616 (Print)
IS  - 2193-9616 (Electronic)
IS  - 2193-9616 (Linking)
VI  - 1
DP  - 2013
TI  - Modeling bioavailability to organs protected by biological barriers.
PG  - 8
LID - 10.1186/2193-9616-1-8 [doi]
LID - 8
AB  - Computational pharmacokinetic (PK) modeling gives access to drug concentration 
      vs. time profiles in target organs and allows better interpretation of clinical 
      observations of therapeutic or toxic effects. Physiologically-based PK (PBPK) 
      models in particular, based on mechanistic descriptions of the body anatomy and 
      physiology, may also help to extrapolate in vitro or animal data to human. Once 
      in the systemic circulation, a chemical has access to the microvasculature of 
      every organ or tissue. However, its penetration in the brain, retina, thymus, 
      spinal cord, testis, placenta,... may be limited or even fully prevented by dynamic 
      physiological blood-tissue barriers. Those barriers are both physical (involving 
      tight junctions between adjacent cells) and biochemical (involving metabolizing 
      enzymes and transporters). On those cases, correct mechanistic characterization 
      of the passage (or not) of molecules through the barrier can be crucial for 
      improved PBPK modeling and prediction. In parallel, attempts to understand and 
      quantitatively characterize the processes involved in drug penetration of 
      physiological barriers have led to the development of several in vitro 
      experimental models. Data from such assays are very useful to calibrate PBPK 
      models. We review here those in vitro and computational models, highlighting the 
      challenges and perspectives for in vitro and computational models to better 
      assess drug availability to target tissues.
FAU - Quignot, Nadia
AU  - Quignot N
AD  - Bioengineering Department, Chair of Mathematical Modeling for Systems Toxicology, 
      Universite de Technologie de Compiegne, Royallieu Research Center, Compiegne, 
      60200 France ; LA-SER, Strategy and Decision Analytics, 10 place de la Catalogne, 
      Paris, 75014 France.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130531
PL  - Germany
TA  - In Silico Pharmacol
JT  - In silico pharmacology
JID - 101623954
PMC - PMC4230447
OTO - NOTNLM
OT  - Bioavailability
OT  - Biological barriers
OT  - Computational model
OT  - PBPK modeling
OT  - Pharmacokinetics
EDAT- 2013/01/01 00:00
MHDA- 2013/01/01 00:01
PMCR- 2013/05/31
CRDT- 2014/12/16 06:00
PHST- 2013/01/02 00:00 [received]
PHST- 2013/05/05 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2013/01/01 00:00 [pubmed]
PHST- 2013/01/01 00:01 [medline]
PHST- 2013/05/31 00:00 [pmc-release]
AID - 8 [pii]
AID - 10.1186/2193-9616-1-8 [doi]
PST - epublish
SO  - In Silico Pharmacol. 2013 May 31;1:8. doi: 10.1186/2193-9616-1-8. eCollection 
      2013.