PMID- 30201539
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 99
DP  - 2018 Nov
TI  - Structural and functional pharmacokinetic analogs for physiologically based 
      pharmacokinetic (PBPK) model evaluation.
PG  - 61-77
LID - S0273-2300(18)30230-7 [pii]
LID - 10.1016/j.yrtph.2018.09.008 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) models enable simulations of 
      absorption, distribution, metabolism, and elimination of chemicals from the body. 
      Model evaluation is a key step in the PBPK model development processes whereby 
      model predictions are compared to pharmacokinetic (PK) data. A prerequisite for 
      PBPK model evaluation has always been the availability of PK data for the modeled 
      compound, a requirement which has limited the use and acceptance of PBPK models 
      since PK data is often limited or not available. The current work tests the 
      hypothesis that an adequately developed PBPK model for a target chemical 
      (chemical with no PK data) can be evaluated using PK data from a source chemical 
      (chemical with existing PK data). Two different approaches for identifying the 
      source chemical, a structural PK analog and functional PK analog technique, are 
      used to evaluate a series of oral human PBPK models. Results show that both 
      analog approaches can identify PK analogs which display similar PK as the target 
      chemical and can be used as alternative ways for evaluating PBPK models. As 
      animal free safety assessment strategies continue to develop, it's important to 
      develop alternative approaches for PBPK model evaluation which does not rely on 
      generating new PK data.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Ellison, Corie A
AU  - Ellison CA
AD  - The Procter & Gamble Company, 8700 Mason Montgomery Road, Cincinnati, OH, 45040, 
      USA. Electronic address: Ellison.ca@pg.com.
LA  - eng
PT  - Journal Article
DEP - 20180908
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Models, Biological
MH  - Pharmaceutical Preparations/*chemistry/*metabolism
MH  - Pharmacokinetics
MH  - Risk Assessment
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Analog
OT  - Modeling
OT  - Pharmacokinetics
OT  - Physiologically based pharmacokinetics
OT  - Read across
OT  - Structural activity relationship
EDAT- 2018/09/12 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/09/12 06:00
PHST- 2018/08/13 00:00 [received]
PHST- 2018/09/05 00:00 [revised]
PHST- 2018/09/06 00:00 [accepted]
PHST- 2018/09/12 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/09/12 06:00 [entrez]
AID - S0273-2300(18)30230-7 [pii]
AID - 10.1016/j.yrtph.2018.09.008 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2018 Nov;99:61-77. doi: 10.1016/j.yrtph.2018.09.008. 
      Epub 2018 Sep 8.