TY - JOUR
T1 - Physiologically based pharmacokinetics of zearalenone
AU - Shin, Beom
AU - Hong, Seok
AU - Bulitta, Jurgen
AU - Lee, Jong
AU - Hwang, Sang
AU - Kim, Hyoung
AU - Yang, Seung
AU - Yoon, Hae-Seong
AU - Kim, Do
AU - Lee, Byung
AU - Yoo, Sun
PY - 2009
Y1 - 2009
N2 - The objectives of this study were to (1) develop physiologically
based pharmacokinetic (PBPK) models for zearalenone following
intravenous (iv) and oral (po) dosing in rats and (2) predict
concentrations in humans via interspecies scaling. The model for
iv dosing consisted of vein, artery, lung, liver, spleen, kidneys,
heart, testes, brain, muscle, adipose tissue, stomach, and small
intestine. To describe the secondary peak phenomenon observed
after po administration, the absorption model was constructed to
reflect glucuronidation, biliary excretion, enterohepatic recirculation,
and fast and slow absorption processes from the lumenal
compartment. The developed models adequately described
observed concentrationa??time data in rats after iv or po administration.
Upon model validation in rats, steady-state zearalenone
concentrations in blood and tissues were simulated for rats after
once daily po exposures (0.1 mg/kg/d). The average steady-state
blood zearalenone concentration predicted in rat was 0.014 ng/ml.
Subsequently, a daily human po dose needed to achieve the same
steady-state blood concentration found in rats (0.014 ng/ml) was
determined to be 0.0312 mg/kg/d or 2.18 mg/70 kg/d. The steadystate
zearalenone concentrationa??time profiles in blood and tissues
were also simulated for human after multiple po administrations
(dose 0.0312 mg/kg/d). The developed PBPK models adequately
described the pharmacokinetics in rats and may be useful in
predicting human blood and tissue concentrations for zearalenone
under different po exposure conditions.
AB - The objectives of this study were to (1) develop physiologically
based pharmacokinetic (PBPK) models for zearalenone following
intravenous (iv) and oral (po) dosing in rats and (2) predict
concentrations in humans via interspecies scaling. The model for
iv dosing consisted of vein, artery, lung, liver, spleen, kidneys,
heart, testes, brain, muscle, adipose tissue, stomach, and small
intestine. To describe the secondary peak phenomenon observed
after po administration, the absorption model was constructed to
reflect glucuronidation, biliary excretion, enterohepatic recirculation,
and fast and slow absorption processes from the lumenal
compartment. The developed models adequately described
observed concentrationa??time data in rats after iv or po administration.
Upon model validation in rats, steady-state zearalenone
concentrations in blood and tissues were simulated for rats after
once daily po exposures (0.1 mg/kg/d). The average steady-state
blood zearalenone concentration predicted in rat was 0.014 ng/ml.
Subsequently, a daily human po dose needed to achieve the same
steady-state blood concentration found in rats (0.014 ng/ml) was
determined to be 0.0312 mg/kg/d or 2.18 mg/70 kg/d. The steadystate
zearalenone concentrationa??time profiles in blood and tissues
were also simulated for human after multiple po administrations
(dose 0.0312 mg/kg/d). The developed PBPK models adequately
described the pharmacokinetics in rats and may be useful in
predicting human blood and tissue concentrations for zearalenone
under different po exposure conditions.
U2 - 10.1080/15287390903212741
DO - 10.1080/15287390903212741
M3 - Article
SN - 1528-7394
VL - 72
SP - 1395
EP - 1405
JO - Journal of Toxicology and Environmental Health, Part A: Current Issues
JF - Journal of Toxicology and Environmental Health, Part A: Current Issues
ER -