Sigler R E, Gough A W, de la Iglesia F A
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Toxicology. 1995 Apr 12;98(1-3):73-82. doi: 10.1016/0300-483x(94)02966-x.
Gabapentin, an anticonvulsant agent designated chemically as 1-(aminomethyl)-cyclohexaneacetic acid, was evaluated in a 2-year tumor bioassay in male Wistar rats. Three groups of 50 rats were fed gabapentin at 250, 1000 and 2000 mg/kg in the diet for 104 weeks. A fourth group was fed diet without drug. All rats were subjected to full histopathological evaluation. Body weight gain suppression occurred at 1000 and 2000 mg/kg. Survival was comparable across all groups. There was a treatment-related increase in the number of pancreatic acinar cell carcinomas; 0, 4, 3 and 8 of these carcinomas were observed in the control, 250, 1000 and 2000 mg/kg groups, respectively. There were no other increases in other tumor types, and there were no tumor increases in female rats. The frequency of pancreatic acinar cell hyperplasia was similar in treated and control groups. Biologically, the pancreatic carcinomas were not invasive, did not metastasize, were of late onset and did not compromise survival. Thus, gabapentin was a carcinogen in male Wistar rats. However, the tumorigenic response was of low-grade because it constituted a late tumor response which required very high doses. We reported recently that mice treated with gabapentin had no increase in pancreatic tumors. Therefore, neoplastic development was confined to the pancreas in a single sex and species of rodent. Consequently, gabapentin at therapeutic doses poses a low carcinogenic risk to humans.
加巴喷丁是一种化学名为1-(氨甲基)环己烷乙酸的抗惊厥药，在一项针对雄性Wistar大鼠的为期两年的肿瘤生物测定中进行了评估。三组各50只大鼠在饮食中分别摄入250、1000和2000 mg/kg的加巴喷丁，持续104周。第四组喂食不含药物的饮食。所有大鼠均接受全面的组织病理学评估。在1000和2000 mg/kg剂量下出现体重增加抑制。所有组的存活率相当。胰腺腺泡细胞癌的数量出现与治疗相关的增加；在对照组、250、1000和2000 mg/kg组中分别观察到0、4、3和8例此类癌症。其他肿瘤类型没有其他增加，雌性大鼠也没有肿瘤增加。治疗组和对照组胰腺腺泡细胞增生的频率相似。从生物学角度来看，胰腺癌没有侵袭性、不发生转移、发病较晚且不影响生存。因此，加巴喷丁在雄性Wistar大鼠中是一种致癌物。然而，致瘤反应程度较低，因为它是一种晚期肿瘤反应，需要非常高的剂量。我们最近报道，用加巴喷丁治疗的小鼠胰腺肿瘤没有增加。因此，肿瘤发生仅限于单一性别和种类的啮齿动物的胰腺。因此，治疗剂量的加巴喷丁对人类构成的致癌风险较低。
