PHYSIOLOGICALLY BASED PHARMACOKINETICS OF BISPHENOL A

Abstract

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), V _ss (141.8 L), and t _1/2 (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.

This work was supported by NITR/Korea FDA grant ED2002-0054 for Endocrine Disrupters Research and in part by the Century 21 Frontier Research Program grant CBM-02-B-8 from the Ministry of Science and Technology, Korea.