Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health

Abstract

Background: AOD9604 is the C-terminal fragment (Tyr-hGH177-191) of human growth hormone (hGH). Early stage studies with AOD9604 have shown positive activities on fat metabolism. As a result the use of AOD9604 to improve metabolic profiles may be plausible. For these uses, the safety of AOD9604 needs to be clearly demonstrated. Here we report the findings from studies involving the genotoxicological, toxicological and pharmacokinetic testing of AOD9604. Methods: In an Ames test, the mutagenic potential of AOD9604 was assessed. A chromosomal aberration assay in CHO cells was used to test the mutagenic activity of AOD9604 by its ability to cause structural damage to chromosomes. A bone micronucleus assay incorporated in a 4-week rat intravenous (IV) toxicity study was used to test potential micronucleus formation. In chronic toxicology studies in rats (6 months) and cynomolgus monkeys (9 months), the potential toxicity of AOD9604 was assessed after daily oral gavage. Pharmacokinetic properties of AOD9604 were examined in a study with pigs after oral and IV administration, and rat whole- body radiography after IV and oral 14 C-AOD9604 application. Results: AOD9604 was found to be generally safe after chronic oral application in rats and cynomolgus monkeys. There was no evidence of any genotoxic activities of AOD9604, as examined in an Ames test, a chromosomal aberration assay, or a bone micronucleus assay. Rat whole- body radiography revealed similar organ distribution after IV or oral application. Orally administered AOD9604 in pigs was well absorbed and results revealed rapid degradation kinetics. Conclusion: Multiple non-clinical studies revealed no evidence of genotoxicological or toxicological concerns regarding the safety of AOD9604. J Endocrinol Metab. 2014;4(3):64-77 doi: http://dx.doi.org/10.14740/jem213w