PANCREATIC ACINAR CELL NEOPLASIA IN MALE WISTAR RATS FOLLOWING 2 YEARS OF GABAPENTIN EXPOSURE

Citation
Re. Sigler et al., PANCREATIC ACINAR CELL NEOPLASIA IN MALE WISTAR RATS FOLLOWING 2 YEARS OF GABAPENTIN EXPOSURE, Toxicology, 98(1-3), 1995, pp. 73-82
Citations number
35
Categorie Soggetti
Toxicology,"Pharmacology & Pharmacy
Journal title
ISSN journal
0300483X
Volume
98
Issue
1-3
Year of publication
1995
Pages
73 - 82
Database
ISI
SICI code
0300-483X(1995)98:1-3<73:PACNIM>2.0.ZU;2-5
Abstract
Gabapentin, an anticonvulsant agent designated chemically as 1-(aminom ethyl)-cyclohexaneacetic acid, was evaluated in a 2-year tumor bioassa y 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 histopathologi cal evaluation. Body weight gain suppression occurred at 1000 and 2000 mg/kg. Survival was comparable across all groups. There was a treatme nt-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 increas es in other tumor types, and there were no tumor increases in female r ats. The frequency of pancreatic acinar cell hyperplasia was similar i n 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 c onstituted a late tumor response which required very high doses. We re ported recently that mice treated with gabapentin had no increase in p ancreatic tumors. Therefore, neoplastic development was confined to th e pancreas in a single sex and species of rodent. Consequently, gabape ntin at therapeutic doses poses a low carcinogenic risk to humans.