Predicting the emetic liability of novel chemical entities: a comparative study

Background and purpose: Emesis is a multi-system reflex, which is usually investigated using in vivo models. The aim of the study is to compare the response induced by emetic compounds across species and investigate whether dogs, ferrets and rats are all similarly predictive of humans.

Experimental approach: A systematic review was carried out and relevant publications were identified from PubMed. The search was restricted to four species (human, dog, ferret, rat) and ten compounds representative of various mechanisms of emesis induction (apomorphine, cisplatin, cholecystokinin octapeptide, copper sulphate, cyclophosphamide, ipecacuanha, lithium chloride, morphine, nicotine, rolipram).

Key results: 1046 publications were reviewed, and 311 were included, the main reason for exclusion was the lack of quantitative data. Emetic or pica data were extracted as incidence, intensity or latency. All three animal species identified emetic liability but interspecies differences for dose sensitivity were detected.

Conclusions and implication: These results suggest that emetic liability can be reliably identified in a common laboratory species such as the rat. However, to evaluate the characteristics of the emetic response, no animal species is a universal predictor of emetic liability and the choice of species should be an informed decision based on the type of compound investigated. Limitations relating to the conduct and reporting of emesis studies were identified, the main ones being the lack of comparable outcome measures between human and animal data, and the limited availability of human data in the public domain.