PMID- 27473014
OWN - NLM
STAT- MEDLINE
DCOM- 20170523
LR  - 20181113
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 307
DP  - 2016 Sep 15
TI  - A simple physiologically based pharmacokinetic model evaluating the effect of 
      anti-nicotine antibodies on nicotine disposition in the brains of rats and 
      humans.
PG  - 150-164
LID - S0041-008X(16)30209-5 [pii]
LID - 10.1016/j.taap.2016.07.017 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) modeling was applied to investigate 
      the effects of anti-nicotine antibodies on nicotine disposition in the brains of 
      rats and humans. Successful construction of both rat and human models was 
      achieved by fitting model outputs to published nicotine concentration time course 
      data in the blood and in the brain. Key parameters presumed to have the most 
      effect on the ability of these antibodies to prevent nicotine from entering the 
      brain were selected for investigation using the human model. These parameters, 
      which included antibody affinity for nicotine, antibody cross-reactivity with 
      cotinine, and antibody concentration, were broken down into different, 
      clinically-derived in silico treatment levels and fed into the human PBPK model. 
      Model predictions suggested that all three parameters, in addition to smoking 
      status, have a sizable impact on anti-nicotine antibodies' ability to prevent 
      nicotine from entering the brain and that the antibodies elicited by current 
      human vaccines do not have sufficient binding characteristics to reduce brain 
      nicotine concentrations. If the antibody binding characteristics achieved in 
      animal studies can similarly be achieved in human studies, however, nicotine 
      vaccine efficacy in terms of brain nicotine concentration reduction is predicted 
      to meet threshold values for alleviating nicotine dependence.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Saylor, Kyle
AU  - Saylor K
AD  - Department of Biological Systems Engineering, Virginia Tech, Seitz Hall, RM 210, 
      155 Ag Quad Lane, Blacksburg, VA 24061, USA. Electronic address: saylor@vt.edu.
FAU - Zhang, Chenming
AU  - Zhang C
AD  - Department of Biological Systems Engineering, Virginia Tech, Seitz Hall, RM 210, 
      155 Ag Quad Lane, Blacksburg, VA 24061, USA. Electronic address: chzhang2@vt.edu.
LA  - eng
GR  - U01 DA036850/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160726
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antibodies)
RN  - 0 (Vaccines)
RN  - 6M3C89ZY6R (Nicotine)
RN  - K5161X06LL (Cotinine)
SB  - IM
MH  - Animals
MH  - Antibodies/*blood
MH  - Brain/*metabolism
MH  - Cotinine/immunology
MH  - Humans
MH  - *Models, Biological
MH  - Nicotine/blood/*immunology/*pharmacokinetics
MH  - Rats
MH  - Smoking/metabolism
MH  - Tissue Distribution
MH  - *Vaccines
PMC - PMC5344185
MID - NIHMS850777
OTO - NOTNLM
OT  - Anti-nicotine antibodies
OT  - Nicotine dependence
OT  - Nicotine disposition
OT  - Nicotine vaccine
OT  - PBPK
OT  - Physiologically based pharmacokinetic model
COIS- Conflict of interest statement The authors declare that they have no conflicting 
      interests.
EDAT- 2016/07/31 06:00
MHDA- 2017/05/24 06:00
PMCR- 2017/09/15
CRDT- 2016/07/31 06:00
PHST- 2016/05/09 00:00 [received]
PHST- 2016/07/22 00:00 [revised]
PHST- 2016/07/25 00:00 [accepted]
PHST- 2016/07/31 06:00 [entrez]
PHST- 2016/07/31 06:00 [pubmed]
PHST- 2017/05/24 06:00 [medline]
PHST- 2017/09/15 00:00 [pmc-release]
AID - S0041-008X(16)30209-5 [pii]
AID - 10.1016/j.taap.2016.07.017 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2016 Sep 15;307:150-164. doi: 10.1016/j.taap.2016.07.017. 
      Epub 2016 Jul 26.