Shin Beom Soo, Kim Chul Hwan, Jun Yoon Sik, Kim Dong Hwan, Lee Byung Mu, Yoon Chi Ho, Park Eun Hye, Lee Kang Choon, Han Soon-Young, Park Kui Lea, Kim Hyung Sik, Yoo Sun Dong
College of Pharmacy, Sungkyunkwan University, Kyonggi-do, Korea.
J Toxicol Environ Health A. 2004 Dec;67(23-24):1971-85. doi: 10.1080/15287390490514615.
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.
建立了一个基于生理的药代动力学（PBPK）模型，该模型由静脉、动脉、肺、肝、脾、肾、心脏、睾丸、肌肉、脑、脂肪组织、胃和小肠组成，用于预测双酚A在大鼠和人类体内的组织分布及血液药代动力学。为证明所建立的PBPK模型的有效性，通过多次静脉注射将双酚A给予大鼠直至稳态。该PBPK模型预测了多次静脉注射后大鼠血液和各种组织中双酚A的稳态水平。该PBPK模型进一步应用于预测单次静脉注射（5毫克剂量）和多次口服给药至稳态（每24小时100毫克剂量）后70千克人体中双酚A的血液和各种组织水平。模拟的人体稳态血液水平（0.9 - 1.6纳克/毫升）与文献报道的双酚A基础血液水平（1.49纳克/毫升）相当。此外，预测的人体药代动力学参数CL（116.6升/小时）、Vss（141.8升）和t1/2（76.8分钟）与先前通过简单的异速生长比例预测的结果相当。该PBPK模型可为人类接触双酚A后的组织分布特征提供见解。
