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猕猴(食蟹猴)血液中甲基汞的药代动力学

Pharmacokinetics of methylmercury in the blood of monkeys (Macaca fascicularis).

作者信息

Rice D C, Krewski D, Collins B T, Willes R F

机构信息

Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.

出版信息

Fundam Appl Toxicol. 1989 Jan;12(1):23-33. doi: 10.1016/0272-0590(89)90058-4.

Abstract

Statistical analysis of the blood mercury profiles of groups of two and four adult female cynomolgus monkeys (Macaca fascicularis) given single oral doses of 500 micrograms and 50 microCi (25.3 micrograms) methylmercury/kg body wt, respectively, indicates that a two-compartment model best describes the absorption and elimination of methylmercury in blood. Absorption was largely complete within 6 hr, and the half-time of methylmercury during the terminal elimination phase ranged from 10 to 15 days. In addition, three groups of five adult female cynomolgus monkeys were dosed with methylmercury every Monday, Wednesday, and Friday for periods up to 2 years at effective doses of 10, 25, or 50 micrograms methylmercury/kg body wt/day. The average blood levels at steady state were estimated to be 0.27 +/- 0.02, 0.69 +/- 0.03, and 1.51 +/- 0.08 ppm, respectively, with average time taken to achieve 95% of the steady-state blood level being about 92 days. The steady-state blood levels obtained via extrapolation of the results from the two single-dose experiments were significantly different from those actually achieved, indicating that the average steady-state blood levels under chronic dosing conditions may not be accurately estimated on the basis of short-term experiments. The data were also used to examine the impact of different dosing intervals on variation in blood mercury levels.

摘要

对分别单次口服500微克/千克体重和50微居里(25.3微克)甲基汞的两组和四组成年雌性食蟹猴(猕猴)血液汞谱进行统计分析表明,二室模型最能描述血液中甲基汞的吸收和消除情况。吸收在6小时内基本完成,终末消除阶段甲基汞的半衰期为10至15天。此外,三组每组五只成年雌性食蟹猴每周一、三、五接受甲基汞给药,持续2年,有效剂量分别为10、25或50微克甲基汞/千克体重/天。稳态时的平均血液水平估计分别为0.27±0.02、0.69±0.03和1.51±0.08 ppm,达到稳态血液水平95%所需的平均时间约为92天。通过对两个单剂量实验结果进行外推得到的稳态血液水平与实际达到的水平有显著差异,这表明基于短期实验可能无法准确估计慢性给药条件下的平均稳态血液水平。这些数据还用于研究不同给药间隔对血液汞水平变化的影响。

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