Subchronic oral toxicity of salcaprozate sodium (SNAC) in Sprague-Dawley and Wistar rats.

Salcaprozate sodium (SNAC) (sodium 8-((2-hydroxybenzoyl) amino) octanoate, CAS RN 203787-91-1) is classified as an oral absorption promoter, and its potential therapeutic applications as a delivery agent for oral forms of heparin and insulin have been explored in a number of clinical investigations. However, limited information about its nonclinical safety is available in the published scientific literature. As part of a larger study exploring the safety of SNAC in combination with heparin, Sprague-Dawley (SD) rats (20/sex/group) received SNAC alone at 2000 mg/kg/d orally (gavage) for 13 weeks (females were terminated after 10 weeks). In a separate study assessing the safety of SNAC in combination with ibandronate, Wistar rats (10/sex/group) received SNAC alone at levels of 100, 500, or 1000 mg/kg/d orally for 13 weeks. SNAC-related mortality was evident only at the 2000-mg/kg/d level, 20% among males and 50% among females; no clear cause of death was evident. No mortality was seen in the Wistar rat study at doses up to 1000 mg/kg/d. Some differences in clinical pathology parameters, including slightly altered electrolyte levels and lower globulin levels, were seen in SD and Wistar rats. Although these differences reached statistical significance, parameters were within historical control ranges. Liver and kidney weights were slightly higher in SNAC-treated animals of both strains, with no corresponding histopathological changes. These changes may therefore constitute an adaptive response. Histopathological changes were seen in the stomach in both studies, probably secondary to irritation caused by the dosing method. Based on the results of these studies, a no-observed-adverse-effect level (NOAEL) cannot be given for SD rats. The NOAEL for SNAC in Wistar rats was considered to be 1000 mg/kg/d.