School of Architecture and Art, Central South University , Changsha, HN, China.
XiangYa School of Public Health, Central South University , Changsha, China.
Int J Environ Health Res. 2021 Mar;31(2):202-214. doi: 10.1080/09603123.2019.1640355. Epub 2019 Jul 12.
Age-specific differences in the pharmacokinetics of benzo(a)pyrene (BaP) and its metabolite 3-hydroxybenzo(a)pyrene (3-OHBaP) potentially affect time courses of tissue concentration; however, the quantitative impact of these differences is not well characterized. Our objective was to quantify the effect of age-specific differences in physiological and biochemical parameters on the pharmacokinetics of BaP and 3-OHBaP from newborn at birth to adulthood following inhalation exposure. The time courses of BaP and 3-OHBaP were simulated by using a physiologically based pharmacokinetic model with Advanced Continuous Simulation Language (ACSLX). The concentrations of BaP increased with age in the liver but decreased with age in most tissues, urine, and blood. The concentrations of 3-OHBaP were the highest in the newborns. Our results also showed that the concentration of BaP has almost reached a steady state in the kidney, liver, lung, rapidly perfused tissues, slowly perfused tissues, and skin except for adipose tissues. However, the concentration of 3-OHBaP has reached a steady state in all tissues. This study suggests that age-specific parameters have an effect on the pharmacokinetics of BaP and 3-OHBaP. In particular, tissue concentration in the newborns is higher than other age groups, which indicates that the newborns are susceptible to environmental BaP exposure.
苯并(a)芘（BaP）及其代谢物 3-羟基苯并(a)芘（3-OHBaP）的药代动力学在不同年龄段存在差异，这可能会影响组织浓度的时间过程；然而，这些差异的定量影响尚未得到很好的描述。我们的目的是量化生理和生化参数在特定年龄段的差异对吸入暴露后从新生儿到成年期 BaP 和 3-OHBaP 药代动力学的影响。使用基于生理的药代动力学模型和高级连续模拟语言（ACSLX）来模拟 BaP 和 3-OHBaP 的时间过程。BaP 的浓度随着年龄的增长在肝脏中增加，但在大多数组织、尿液和血液中随着年龄的增长而降低。3-OHBaP 的浓度在新生儿中最高。我们的结果还表明，BaP 的浓度在肾脏、肝脏、肺、快速灌注组织、缓慢灌注组织和皮肤（脂肪组织除外）中几乎达到稳定状态。然而，3-OHBaP 的浓度在所有组织中均达到稳定状态。本研究表明，特定年龄段的参数对 BaP 和 3-OHBaP 的药代动力学有影响。特别是，新生儿组织中的浓度高于其他年龄组，这表明新生儿易受环境 BaP 暴露的影响。
