Equine Drug Transporters: A Mini-Review and Veterinary Perspective

Abstract

Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug–drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.

Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations

“…Recent studies have described the PK at multiple oral CBD doses using hemp pellets and sunflower lecithin oil‐based formulations, but the ranges described are lower than those predicted in this research due to the use of lower doses, and particularly, different formulations, which can influence the oral absorption and bioavailability of CBD as have been described 18,20,44,45,47–49 . This is an important issue in the horse where the oral route is one of the most clinically used, although drug transporters and intestinal permeability are more limited and the absorption is usually lower than in other monogastric species, therefore, it is necessary to study specific oral formulations in equine 51 . On the other hand, IV simulations also have been included in this study even though parenteral routes are not usually preferred for chronic treatment.…”

“…18,20,44,45,[47][48][49] This is an important issue in the horse where the oral route is one of the most clinically used, although drug transporters and intestinal permeability are more limited and the absorption is usually lower than in other monogastric species, therefore, it is necessary to study specific oral formulations in equine. 51 On the other hand, IV simulations also have been included in this study even though parenteral routes are not usually preferred for chronic treatment. However, they can provide useful information as starting points to determine effective plasma concentrations, as well as in preliminary studies of detection times in sport animals, as has recently been described with analgesics and sedatives in horses.…”

Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?

“…In addition to oral bioavailability, it is also important to consider the differences in equine metabolism and its implications on the administered medications. These differences might hinder the application and extrapolation of human medications and other species to horses [ 10 ]. An example is prednisone, a pro-drug that is bio-activated to prednisolone by hepatic enzyme 11-β-hydroxy-dehydrogenase [ 11 ].…”