The Use of Swine in Drug Toxicity Studies*

Earl, Francis L.; Tegeris, Andrew S.; Whitmore, G. E.; Morison, Rutherford; Fitzhugh, O. Garth

doi:10.1111/j.1749-6632.1964.tb53136.x

Cited by 14 publications

(2 citation statements)

References 8 publications

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“…humans with regard to, at least, the nervous and cardiovascular systems and the GIT (Earl et al, 1964), and others have noted that the pig is the accepted model for human dermal studies (e.g., "The minipig is the species of choice to investigate dermal absorption in preclinical drug development"; Preube and Skaanild, 2012). Whereas the GIT blood circulation in the chimpanzee is quite similar to that of humans, Noer (1943) has noted that the circulation in the small intestine of the dog is quite different from humans.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

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

Tang

Mayersohn

2018

Drug Metab Dispos

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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.

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Section: Introduction and Historical Perspectivementioning

confidence: 99%

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

Tang

Mayersohn

2018

Drug Metab Dispos

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“…The pig is physiologically similar to man (Earl et al, 1964;Bustad and McClellan, 1966) and should be a useful test animal.…”

Section: Introductionmentioning

confidence: 99%

Effects of subclinical lead exposure on the resistance of swine to challenge with Salmonella choleraesuis var Kunzendorf

Lassen

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Model of TPN-associated hepatobiliary dysfunction in the young pig

Truskett

Shi

Rose

et al. 1987

Journal of British Surgery

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Gallbladder 'sludge' and cholestasis are two common complications associated with total parenteral nutrition (TPN), but the aetiology of each is uncertain. An animal model has been developed in the young pig which demonstrates these two complications. Five female piglets, of Landrace Large White Cross variety weighing 4.5-5.9 kg, received nutritional support for 2 weeks with a continuous infusion of TPN solution at a dose of 150 kcal kg-1 day-1. The solution was 35 per cent dextrose, 5 per cent L-amino acids with conventional electrolyte, mineral and vitamin additives. No lipid was used in the solution. Five weight-matched animals were used as controls. All animals in the TPN group developed 'sludge' in their gallbladders, decreased basal bile flow, decreased bile salt excretion and a diminished response to bile salt stimulated bile flow, as compared with controls. There was no abnormality in routine liver function tests or liver histology. It is concluded that TPN therapy in this animal model is associated with the appearance of gallbladder 'sludge', and cholestasis as demonstrated by direct bile flow studies. It is suggested that this bile flow abnormality is due to a decrease in bile salt dependent and bile salt independent fractions of canalicular bile flow. The model provides the opportunity to investigate TPN related hepatobiliary dysfunction in an animal that has similar liver function to man and comparable nutritional requirements.

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The Use of Swine in Drug Toxicity Studies*

Cited by 14 publications

References 8 publications

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

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

Effects of subclinical lead exposure on the resistance of swine to challenge with Salmonella choleraesuis var Kunzendorf

Model of TPN-associated hepatobiliary dysfunction in the young pig

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