Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics

Abstract

Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.

Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses

“…Low bioavailability of CBD in horses could be affected by absorption time due to the amount of forage in the gastrointestinal tract, pH variations in the gastrointestinal tract, absorptive surface areas, protein binding, and enzymes specific to the equine digestive tract due to them being hindgut fermenters. [34][35][36] Another potential explanation for differences in kinetic absorption is that horses have different enzymes and protein binding that could have interfered. A protein binding study may be beneficial to be conducted with oral CBD, where it can be determined whether CBD is being bound by the enzymes in senior horses and maybe the free CBD is the only portion being absorbed.…”

The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses

“…Therefore, without additional undue study, the exact cause of this appearance is undetermined. Although we did observe this secondary peak in the fasted state, it is not recommended to fast a horse before drug administration as holding off horses feed overnight and intermittent feeding schedules that produce an empty stomach may be one of the risk factors for equine gastric disease syndrome (Martinez et al., 2022).…”