PMID- 28001497
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20170313
IS  - 1944-0057 (Electronic)
IS  - 1944-0057 (Linking)
VI  - 34
IP  - 2
DP  - 2017 Feb
TI  - Physiologically based pharmacokinetic model for quinocetone in pigs and 
      extrapolation to mequindox.
PG  - 192-210
LID - 10.1080/19440049.2016.1258121 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) models are scientific methods used 
      to predict veterinary drug residues that may occur in food-producing animals, and 
      which have powerful extrapolation ability. Quinocetone (QCT) and mequindox (MEQ) 
      are widely used in China for the prevention of bacterial infections and promoting 
      animal growth, but their abuse causes a potential threat to human health. In this 
      study, a flow-limited PBPK model was developed to simulate simultaneously residue 
      depletion of QCT and its marker residue dideoxyquinocetone (DQCT) in pigs. The 
      model included compartments for blood, liver, kidney, muscle and fat and an extra 
      compartment representing the other tissues. Physiological parameters were 
      obtained from the literature. Plasma protein binding rates, renal clearances and 
      tissue/plasma partition coefficients were determined by in vitro and in vivo 
      experiments. The model was calibrated and validated with several pharmacokinetic 
      and residue-depletion datasets from the literature. Sensitivity analysis and 
      Monte Carlo simulations were incorporated into the PBPK model to estimate 
      individual variation of residual concentrations. The PBPK model for MEQ, the 
      congener compound of QCT, was built through cross-compound extrapolation based on 
      the model for QCT. The QCT model accurately predicted the concentrations of QCT 
      and DQCT in various tissues at most time points, especially the later time 
      points. Correlation coefficients between predicted and measured values for all 
      tissues were greater than 0.9. Monte Carlo simulations showed excellent 
      consistency between estimated concentration distributions and measured data 
      points. The extrapolation model also showed good predictive power. The present 
      models contribute to improve the residue monitoring systems of QCT and MEQ, and 
      provide evidence of the usefulness of PBPK model extrapolation for the same kinds 
      of compounds.
FAU - Zhu, Xudong
AU  - Zhu X
AD  - a MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and 
      Poultry Products , Huazhong Agricultural University , Wuhan , China.
FAU - Huang, Lingli
AU  - Huang L
AD  - a MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and 
      Poultry Products , Huazhong Agricultural University , Wuhan , China.
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Xu, Yamei
AU  - Xu Y
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Xie, Shuyu
AU  - Xie S
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Pan, Yuanhu
AU  - Pan Y
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Chen, Dongmei
AU  - Chen D
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Liu, Zhenli
AU  - Liu Z
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
FAU - Yuan, Zonghui
AU  - Yuan Z
AD  - a MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and 
      Poultry Products , Huazhong Agricultural University , Wuhan , China.
AD  - b National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key 
      Laboratory for Detection of Veterinary Drug Residues , Huazhong Agricultural 
      University , Wuhan , China.
LA  - eng
PT  - Journal Article
DEP - 20161221
PL  - England
TA  - Food Addit Contam Part A Chem Anal Control Expo Risk Assess
JT  - Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & 
      risk assessment
JID - 101485040
RN  - 0 (Mequindox)
RN  - 0 (Quinoxalines)
RN  - 0 (quinocetone)
SB  - IM
MH  - Animals
MH  - Drug Residues/chemistry/metabolism/pharmacokinetics
MH  - *Models, Biological
MH  - Molecular Dynamics Simulation
MH  - Monte Carlo Method
MH  - Quinoxalines/analysis/metabolism/*pharmacokinetics
MH  - Swine/*metabolism
OTO - NOTNLM
OT  - Monte Carlo analysis
OT  - PBPK model
OT  - cross-compound extrapolation
OT  - mequindox
OT  - quinocetone
OT  - residue prediction
EDAT- 2016/12/22 06:00
MHDA- 2017/03/14 06:00
CRDT- 2016/12/22 06:00
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2016/12/22 06:00 [entrez]
AID - 10.1080/19440049.2016.1258121 [doi]
PST - ppublish
SO  - Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017 
      Feb;34(2):192-210. doi: 10.1080/19440049.2016.1258121. Epub 2016 Dec 21.