1.Peri- and Postnatal Developmental Toxicity of Salcaprozate Sodium (SNAC) in Sprague-Dawley Rats
M. Gary I. Riley, Raymond G. York. International Journal of Toxicology Volume 28 Number 4 July/August 2009 266-277
Salcaprozate sodium (SNAC) (sodium 8-((2-hydroxybenzoyl)amino) octanoate, CAS RN 203787-91-1) is classified as an oral absorption promoter. Although several clinical investigations have explored the potential therapeutic applications of SNAC as a delivery agent for oral forms of heparin and insulin, limited information about the nonclinical safety of SNAC itself was found in the published scientific literature. In a published review article on the development of an oral heparin formulation, the results of SNAC toxicological studies are given, but the item provides no details regarding their conduct.
The present report summarizes the findings of a study that examined the effects of SNAC on the gestation, parturition, lactation, maternal behavior, and offspring development of rats. In that study, SNAC was administered to pregnant rats at 0, 500, 750, and 1000 mg/kg/d with 5000 USP units of heparin sodium/d. The study, sponsored by Emisphere Technologies, Inc (Cedar Knolls, New Jersey), involved extensive evaluations and conformed to International Conference on Harmonization (ICH) Harmonized Tripartite Guideline stages C (implantation) through F (lactation and weaning) of the reproductive process. To detect any potential delayed adverse effects resulting from prenatal and perinatal SNACexposure, observations weremade until F1 generation rats reached sexual maturity and F1 females became pregnant. Only the findings from groups treated with SNAC alone or the vehicle (deionized water) are included in the present report because the presence of heparin in other groups might be confounding.Test Substance, Dose Selection, and Dosing.
2. Subchronic Oral Toxicity of Salcaprozate Sodium (SNAC) in Sprague-Dawley and Wistar Rats
M. Gary I. Riley, M. Cristina Castelli, Ellen Angela Paehler. International Journal of Toxicology Volume 28 Number 4 July/August 2009 278-293
The present report summarizes the findings of 2 separate studies that explored the subchronic oral toxicity of SNAC in Sprague-Dawley andWistar rats. The first study, sponsored by Emisphere Technologies, Inc (Cedar Knolls, New Jersey), employed SNAC alone and in combination with heparin. A second study, exploring the toxicity of SNAC alone and in combination with ibandronate, was sponsored by F. Hoffmann–LaRoche Ltd under
a development and license agreement with Emisphere. For both studies, only the findings from
groups treated with SNAC alone or the vehicle (deionized water) are included in this report because it would be difficult to distinguish SNAC-related effects from drug-related effects in SNAC-heparin and SNAC-ibandronate groups.