Experimental studies on the long-term effects of methylphenidate hydrochloride
Experimental studies on the long-term effects of methylphenidate hydrochloride
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DOI：
10.1016/0300-483x(95)03109-s
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发表时间：
1995-11-30
期刊：
影响因子：
4.5
通讯作者：
Hailey, JR
中科院分区：
文献类型：
--
作者：
Dunnick, JK;Hailey, JR
在F344大鼠和B6 C3 F1小鼠中进行了盐酸哌甲酯（一种用于治疗注意力缺陷障碍的药物）的毒理学和致癌性研究。在这些研究中，在由50只动物/剂量/性别/种属组成的组中，以0、100、500或1000 ppm的剂量在大鼠饲料中给予盐酸哌甲酯2年，并以0、50、250、500 ppm的剂量给予小鼠2年。大鼠和小鼠每天消耗的哌甲酯平均量估计分别为4-47 mg/kg/天和5-67 mg/kg/天。给药组和对照组的生存率相似。在高剂量组雄性和雌性小鼠中观察到肝脏良性肿瘤增加和肝脏重量增加。在高剂量雄性小鼠中也观察到肝母细胞瘤增加。哌醋甲酯在沙门氏菌试验系统中无致突变性，假设这种致瘤效应可能是由于化学品的非遗传毒性效应，如细胞增殖增加。在大鼠中未观察到肿瘤发生率增加。然而，雌性大鼠乳腺纤维腺瘤显著减少，雄性大鼠良性嗜铬细胞瘤略有减少。哌甲酯的流行病学研究没有发现对人类有致癌作用的证据，就像我们在大鼠中的发现一样，报告了服用哌甲酯的患者的癌症发病率低于预期。
Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate.