Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke?

Abstract

The minipig has become an animal of considerable interest in preclinical drug development. It has been used in toxicology research and in examining/establishing regulatory guidelines as a nonrodent animal model. We have reviewed some basic issues that one would want to consider in the development and testing of any animal model for humans. The pig is a reasonable alternative to the dog, but there are some clear limitations and unexplained disparities in the literature, which require further study; primary among these is the need for standardization in choice of breed and sex and routine protocols. The minipig offers numerous advantages over other established animal models, and it has similarities to the human with regard to anatomy, physiology, and biochemistry. The gastrointestinal tract is structurally and functionally similar to humans. This appears to be true for enzymes and transporters in the gut as well, but more study is needed. One major concern is assessment of oral drug absorption, especially with regard to potential food effects due to gastric emptying differences, yet this does not appear to be a consistent observation. Hepatic metabolism seems to reflect enzymatic patterns in humans, with some differences. Kidney function seems similar to humans but requires further study. We have analyzed literature data that suggest the pig would offer a reasonable model for human oral bioavailability and for allometric predictions of clearance. The minipig appears to be the model for dermal absorption in humans, and we discuss this in terms of literature data and our own in-house experience.

Genetic basis for the cooperative bioactivation of plant lignans by Eggerthella lenta and other human gut bacteria

“…Human data on lignan concentrations are not available; however, pigs are reasonable models of the human GI tract 38 . In pigs fed a lignan-rich diet, ~40% was excreted as enterolignans 39 .…”

Influence of extracorporeal membrane oxygenation on the pharmacokinetics of ceftolozane/tazobactam: an ex vivo and in vivo study

“…For the in vivo experiments, a porcine model was chosen because of anatomical similarities (vascular volume, blood flow, etc. ), which provided pigs compatible with the human adult ECMO device, and with physiological similarities that make them an interesting human pharmacokinetic model [20,21]. A two-compartment model was selected for both ceftolozane and tazobactam as was the case in studies performed in humans [22,23].…”

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

“…Moreover, differences in between breeds exist [257] and, since fully characterizing all the pig breeds available is a long-term task, most efforts concentrate in studying the most used pig breed in pharmacological studies in Europe, the Göttingen Minipig [35,[43][44][45][258][259][260][261][262][263][264][265][266][267][268][269][270][271][272][273][274]. Inter-breed differences are magnified due to the lack of standardization regarding food and feeding patterns, age and sex of pigs used in research [275]. To improve the characterization of the pig, phenotyping techniques and assessment protocols are also needed to enable progress.…”