Miniature Swine Breeds in Toxicology and Drug Safety Assessments

Abstract

The use of miniature swine as a nonrodent species in safety assessment has continued to expand for over a decade, and they are becoming routinely used in toxicology and in pharmacology as well as a model for human diseases. Miniature swine models are regularly used for regulatory toxicity studies designed to assess safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to the canine or the nonhuman primate. Translational preclinical swine study data presented support the current finding that miniature swine are the animal model of choice for assessment of drug absorption, tolerance, and systemic toxicity following systemic exposures. Because research investigators need to be familiar with important anatomic and histopathologic features of the miniature swine in order to place toxicopathologic findings in their proper perspective, clinical and anatomic pathology data from a large number of Sinclair, Hanford, Yucatan, and Gö ttingen breeds from control groups from a wide variety of studies performed between 2004 and 2014 will be presented, compared, and partially illustrated.

Minipigs as models in drug discovery

“…These animals are readily amenable to various methods of drug administration, including inhalation, oral intubation, dietary, dermal, multiple routes of parenteral injections, and continuous intravenous infusion. These characteristics make the minipig similar to both canines and NHPs; however, minipigs are frequently overlooked as an animal model for the pharmacokinetic screenings of drugs [15].…”

“…Minipigs have been used as animal models for several clinical indications such as cardiovascular, metabolic syndromes, digestive (gastric) and bone disorders, diabetes, heart disease, skin conditions, and acute and chronic intestinal inflammation [9,15]. Cardiovascular disease is widely recognized as a common underlying cause of mortality in developed countries, varying with increased prosperity and longevity.…”

Morphological characteristics and notes of the skin in preclinical toxicity assessment

“…In contrast, humans and guinea pigs show a mosaic pattern, with each follicle exhibiting an independent hair cycle 39 , 40 . The density of hair follicles varies with species, with higher follicle densities in rodents and lower densities in humans, monkeys, and minipigs 7 , 9 .…”

“…Guinea pigs have also been used in skin sensitization studies. In recent years, general toxicity studies and irritation evaluations have been conducted using minipigs, whose skin most closely resembles human skin, with similar thicknesses of various layers and hair follicle density 6 , 7 , 8 . This review summarizes the histopathological characteristics of each part of the skin, such as the epidermis, dermis, subcutaneous tissue, and adnexa, as well as species differences, mechanisms of skin injury, and notes on tissue preparation.…”

The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform

“…Swine are not typically used during early drug development because of their large mass and the relative lack of drug until production scales up ( 138 ). However, swine have been used in safety assessment and are increasingly used because of similarities to humans in cardiovascular anatomy and physiology, integumentary system, digestive system, renal system, and immune system ( 139 ). The porcine PXR gene regulates hepatic genes involved in metabolism and transport.…”