Physiologically based pharmacokinetics of bisphenol A.
A physiologically based pharmacokinetic (PBPK) model consisting of vein, artery, lung, liver, spleen, kidneys, heart, testes, muscle, brain, adipose tissue, stomach, and small intestine was developed to predict the tissue distribution and blood pharmacokinetics of bisphenol A in rats and humans. To demonstrate the validity of the developed PBPK model, bisphenol A was administered to rats by multiple iv injections to steady state. The PBPK model predicted the steady-state levels of bisphenol A in blood and various tissues observed in rats after multiple iv injections. The PBPK model was further applied to predict blood and various tissue levels of bisphenol A in a 70 kg-human after single iv injection (5-mg dose) and multiple oral administrations to steady state (100-mg doses every 24 h). The simulated steady-state human blood levels (0.9-1.6 ng/ml) were comparable to basal blood levels of bisphenol A reported in literature (1.49 ng/ml). Furthermore, pharmacokinectic parameters of CL (116.6 L/h), Vss (141.8 L), and t1/2 (76.8 min) predicted for humans were comparable to those previously predicted by simple allometric scaling. This PBPK model may provide insights into the tissue distribution characteristics as a result of human exposure to bisphenol A.
Shin
Beom Soo
BS
College of Pharmacy, Sungkyunkwan University, Kyonggi-do, Korea.
Kim
Chul Hwan
CH
Jun
Yoon Sik
YS
Kim
Dong Hwan
DH
Lee
Byung Mu
BM
Yoon
Chi Ho
CH
Park
Eun Hye
EH
Lee
Kang Choon
KC
Han
Soon-Young
SY
Park
Kui Lea
KL
Kim
Hyung Sik
HS
Yoo
Sun Dong
SD
D000818:Animals; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005544:Forecasting; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D010636:Phenols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds