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.
Highlights
The disposition and pharmacokinetics of many drugs are dependent on the activity of transport proteins located within cell membranes
The results of a study examining the pharmacokinetics of the antihistamine fexofenadine, a permeability glycoprotein (P-gp) substrate [54], in horses suggest that organic anion transporting polypeptides (OATPs) may play a role in equine intestinal drug absorption
Knowledge of transporter expression and activity is critical for accurate Physiologically-based pharmacokinetic (PBPK) modeling, and allows differences in transporter expression between animals and cell culture systems to be accounted for during in vitro to in vivo extrapolation of pharmacokinetic parameters [38]
Summary
The disposition and pharmacokinetics of many drugs are dependent on the activity of transport proteins located within cell membranes These transporters move their substrates into and out of cells, and play a critical role in the ADME processes of absorption, distribution, metabolism, and elimination. ABC transporters are ubiquitous transmembrane proteins that use ATP hydrolysis to move substances across cell membranes In addition to their role in drug transport in eukaryotes they play an important role in prokaryotic drug resistance [7], and in multidrug resistant neoplasia [8]. Certain ABC transporters have commonly used human and veterinary drugs as their substrates These transporters include: permeability glycoprotein (P-gp), encoded by the gene ABCB1; breast cancer resistance protein (BCRP), encoded by the gene ABCG2; and several of the multidrug resistance proteins (MRPs), which are encoded by ABCC genes [4]. The pharmacokinetic characteristics of many drugs depend on the interplay between the SLC and ABC transporters of which they are substrates, as well as other metabolic processes, and the physicochemical characteristics of the drug
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