Gallenberg L A, Vodicnik M J
Drug Metab Dispos. 1987 May-Jun;15(3):363-6.
It has been suggested based on fecal elimination data that a second dose of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) is eliminated more rapidly from male rats than a first dose of 6-CB due to a differential accumulation of the two 6-CB doses within individual adipocytes. This phenomenon was further examined and extended to assess tissue levels of the compound in male rats which received either 0.6 mg/kg unlabeled or 14C-6-CB iv (dose 1). Fourteen days later, those animals which had received unlabeled 6-CB were administered 0.6 mg/kg 14C-6-CB. One-half of those rats which had received 14C-6-CB as dose 1 were administered unlabeled 6-CB after 14 days, and the remainder did not receive a second dose. The fecal excretion of radiolabeled 6-CB from rats treated only with 14C-6-CB was 5.3% of the total dose from days 14 through 28 post-treatment. Those rats receiving 14C-6-CB followed by unlabeled 6-CB excreted 4.4% of the total radiolabeled dose. Animals treated with 14C-6-CB as the second dose excreted 9% of their total radiolabeled dose within 14 days of treatment and those receiving only 14C-6-CB excreted 11% over the same time interval. Urinary elimination of radioactivity was negligible in all treatment groups. The pattern of distribution of 14C-6-CB in tissues was similar among all treatment groups. These data suggest that a second dose of 6-CB is not distributed differently from the first in growing male rats.
基于粪便排泄数据表明,由于两种剂量的2,4,5,2',4',5'-六氯联苯(6-CB)在单个脂肪细胞内的差异积累,雄性大鼠体内第二剂量的6-CB比第一剂量的6-CB消除得更快。对这一现象进行了进一步研究并扩展,以评估接受0.6mg/kg未标记的或静脉注射14C-6-CB(剂量1)的雄性大鼠体内该化合物的组织水平。十四天后,给那些接受未标记6-CB的动物注射0.6mg/kg的14C-6-CB。那些接受14C-6-CB作为剂量1的大鼠中有一半在14天后给予未标记的6-CB,其余的则不接受第二剂量。仅用14C-6-CB处理的大鼠,放射性标记的6-CB在处理后第14天至28天的粪便排泄量占总剂量的5.3%。那些先接受14C-6-CB然后接受未标记6-CB的大鼠排泄了总放射性标记剂量的4.4%。用14C-6-CB作为第二剂量处理的动物在处理后的14天内排泄了其总放射性标记剂量的9%,而那些仅接受14C-6-CB的动物在相同时间间隔内排泄了11%。在所有处理组中,尿液中放射性的消除量可忽略不计。所有处理组中14C-6-CB在组织中的分布模式相似。这些数据表明,在生长中的雄性大鼠中,第二剂量的6-CB与第一剂量的分布没有差异。