RT Journal Article
SR Electronic
T1 Porcine Prediction of Pharmacokinetic Parameters in People: A Pig in a Poke?
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1712
OP 1724
DO 10.1124/dmd.118.083311
VO 46
IS 11
A1 Huadong Tang
A1 Michael Mayersohn
YR 2018
UL http://dmd.aspetjournals.org/content/46/11/1712.abstract
AB 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.