Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Acute Toxicity of Vildagliptin: Differences in Sensitivity Between Cynomolgus Monkeys of Asian or Mauritian Origin

Hoffmann, Peter and Keselica, Michael and Gunson, Diane and Lapadula, Daniel (2016) Acute Toxicity of Vildagliptin: Differences in Sensitivity Between Cynomolgus Monkeys of Asian or Mauritian Origin. Toxicol Pathol, 45. pp. 76-83.

Abstract

This paper describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails and face associated with skeletal muscle necrosis, elevations of LDH, CK, ALT and AST activities in the serum, hypothermia, hypotension, tachycardia, moribundity and death in a few isolated instances. In surviving animals symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius are more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data and it is concluded that acute toxicity following vildagliptin treatment is a monkey specific phenomenon without relevance for humans.

Item Type: Article
Date Deposited: 30 Mar 2017 00:45
Last Modified: 30 Mar 2017 00:45
URI: https://oak.novartis.com/id/eprint/29882

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.