Investigation of Minipigs as the Optimal Non-rodent Pre-clinical Species: Exploring Plasma Protein Binding of Marketed Cardiovascular Drugs Across Species

Abstract

Pre-clinical studies in animals are an essential part of drug development for new chemical entities. Before clinical trials in humans, submission of safety data from one rodent and one non-rodent species is compulsory as per regulatory guidelines. Even though minipigs and monkeys are physiologically closer to humans, dogs are usually employed as the non-rodent pre-clinical species. In this study, the in vitro plasma protein binding of eleven marketed cardiovascular drugs was studied in dog, minipig, monkey and human to determine the preferred species. To conduct plasma protein binding studies, the most reliable equilibrium dialysis method was adopted. Ten out of eleven tested cardiovascular drugs showed statistically similar plasma protein binding in minipig and human plasma which was different from dog and monkey plasma. The results from the studies showed greater similarity between minipigs and humans suggesting that the minipig species maybe a better pre-clinical non-rodent model during drug development of cardiovascular drugs instead of the conventional dog species. Additionally, use of the more accessible minipig species may help in saving time, and resources during pre-clinical studies and may also be more predictive during the safety studies in humans during later stage clinical trials.

Graphical Abstract