Sundberg J, Jönsson S, Karlsson M O, Hallén I P, Oskarsson A
Toxicology Division, National Food Administration, Uppsala, Sweden.
Toxicol Appl Pharmacol. 1998 Aug;151(2):319-29. doi: 10.1006/taap.1998.8456.
The elimination of mercury was followed for 9 days (Days 10-19 of lactation) in milk and/or 21 days in blood and plasma of lactating and nonlactating mice administered a single iv injection of either 203Hg-labeled methylmercuric chloride or 203Hg-labeled mercuric chloride (0.5 mg Hg/kg body wt). Demethylation of methylmercury to inorganic mercury was taken into consideration by analyzing the data with a combined pharmacokinetic model based on the assumption of constant blood plasma ratios for methylmercury and inorganic mercury. A three-compartment model fitted the blood and plasma concentrations vs time profiles for both compounds. Plasma clearance and volume of distribution at steady state for methylmercury were 95. 3 ml/h/kg and 18,500 ml/kg, respectively, in lactating mice, and significantly higher than in nonlactating mice with values of 47.1 ml/h/kg and 9400 ml/kg, respectively. The terminal half-lives of methylmercury in plasma were similar, 170 h in lactating and 158 h in nonlactating mice. No differences were observed between the pharmacokinetic parameters in lactating and nonlactating mice administered inorganic mercury. The lactational transfer of mercury was more efficient following administration of inorganic mercury than after administration of methylmercury, with a five times higher peak concentration in milk, higher milk:plasma concentration ratios, and 8% of the administered dose excreted in milk compared with 4% for methylmercury. Mercury concentrations in milk following an iv dose of inorganic mercury decreased with a terminal half-life of 107 h, whereas after administration of methylmercury, the concentration of total mercury in milk remained at an almost constant level during the whole period of investigation. There was a nonlinear relationship between mercury in milk and plasma following inorganic mercury administration. It is suggested that inorganic mercury enters the mammary gland by a carrier-mediated transport system, which is saturated at high plasma levels of inorganic mercury. The present study shows that physiological changes during lactation alter the pharmacokinetics for methylmercury in mice but not for inorganic mercury.
给哺乳期和非哺乳期小鼠单次静脉注射203Hg标记的甲基氯化汞或203Hg标记的氯化汞（0.5毫克汞/千克体重）后，在其乳汁中追踪汞的消除情况9天（哺乳期第10 - 19天），在血液和血浆中追踪21天。通过基于甲基汞和无机汞血浆比例恒定的假设，用联合药代动力学模型分析数据，考虑了甲基汞向无机汞的去甲基化过程。三室模型拟合了两种化合物的血液和血浆浓度随时间变化的曲线。哺乳期小鼠中，甲基汞的血浆清除率和稳态分布容积分别为95.3毫升/小时/千克和18500毫升/千克，显著高于非哺乳期小鼠，后者的值分别为47.1毫升/小时/千克和9400毫升/千克。甲基汞在血浆中的终末半衰期相似，哺乳期小鼠为170小时，非哺乳期小鼠为158小时。给无机汞的哺乳期和非哺乳期小鼠的药代动力学参数之间未观察到差异。与甲基汞相比，给予无机汞后汞的泌乳转运更有效，乳汁中的峰值浓度高五倍，乳汁与血浆的浓度比更高，给药剂量的8%经乳汁排泄，而甲基汞为4%。静脉注射无机汞后乳汁中的汞浓度以107小时的终末半衰期下降，而给予甲基汞后，整个研究期间乳汁中总汞浓度几乎保持恒定。给予无机汞后，乳汁和血浆中的汞之间存在非线性关系。提示无机汞通过载体介导的转运系统进入乳腺，该系统在无机汞血浆水平较高时会饱和。本研究表明，哺乳期的生理变化改变了小鼠体内甲基汞的药代动力学，但未改变无机汞的药代动力学。
