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The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmacodynamic drug testing

Elke Gasthuys (UGent) , Tim Vandecasteele (UGent) , Pauline De Bruyne (UGent) , Johan Vande Walle (UGent) , Patrick De Backer (UGent) , Pieter Cornillie (UGent) , Mathias Devreese (UGent) and Siska Croubels (UGent)
(2016) CURRENT PHARMACEUTICAL DESIGN. 22(26). p.4069-4085
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Abstract
Pediatric drug research is still substandard, not reaching the same quality level as adult drug research. Despite the efforts made by the Food and Drug Administration and European Medicines Agency to reduce off-label use in children, the lack of clinical studies involving the pediatric population still stands. Pharmacokinetic and pharmacodynamics studies (PK/PD) taking growth and maturation into account are necessary to rationalize dosing strategies in children. Currently, traditional animal models such as rats, mice, dogs and primates are used to conduct pharmacokinetic and pharmacodynamic studies, however age-related trials are rather uncommon. Moreover, these species have several shortcomings as animal models, such as a different physiology and anatomy of the gastrointestinal tract in dogs or the ethical aspects for the use of primates. In contrast, piglets might be potential biomedical pediatric animal models because of the good resemblance with humans, anatomically, physiologically and biochemically. This review summarizes the comparative anatomy and physiology and postnatal development of piglets and infants, focusing on six major topics, namely growth, cardiovascular system, gastrointestinal tract, liver, kidney and integument. Furthermore, the application of piglets as animal model in pediatric PK/PD research is discussed.
Keywords
piglet., physiology, pharmacokinetic, pediatric, ontogeny, drug design, Animal model, anatomy, BROWN ADIPOSE-TISSUE, PANCREATIC EXOCRINE SECRETION, GLOMERULAR-FILTRATION-RATE, POSTNATAL-DEVELOPMENT, SMALL-INTESTINE, BODY-COMPOSITION, DOMESTIC PIG, NEWBORN PIGLETS, RENAL-FUNCTION, HUMAN LIVER

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Chicago
Gasthuys, Elke, Tim Vandecasteele, Pauline De Bruyne, Johan Vande Walle, Patrick De Backer, Pieter Cornillie, Mathias Devreese, and Siska Croubels. 2016. “The Potential Use of Piglets as Human Pediatric Surrogate for Preclinical Pharmacokinetic and Pharmacodynamic Drug Testing.” Current Pharmaceutical Design 22 (26): 4069–4085.
APA
Gasthuys, E., Vandecasteele, T., De Bruyne, P., Vande Walle, J., De Backer, P., Cornillie, P., Devreese, M., et al. (2016). The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmacodynamic drug testing. CURRENT PHARMACEUTICAL DESIGN, 22(26), 4069–4085.
Vancouver
1.
Gasthuys E, Vandecasteele T, De Bruyne P, Vande Walle J, De Backer P, Cornillie P, et al. The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmacodynamic drug testing. CURRENT PHARMACEUTICAL DESIGN. 2016;22(26):4069–85.
MLA
Gasthuys, Elke, Tim Vandecasteele, Pauline De Bruyne, et al. “The Potential Use of Piglets as Human Pediatric Surrogate for Preclinical Pharmacokinetic and Pharmacodynamic Drug Testing.” CURRENT PHARMACEUTICAL DESIGN 22.26 (2016): 4069–4085. Print.
@article{8046304,
  abstract     = {Pediatric drug research is still substandard, not reaching the same quality level as adult drug research. Despite the efforts made by the Food and Drug Administration and European Medicines Agency to reduce off-label use in children, the lack of clinical studies involving the pediatric population still stands. Pharmacokinetic and pharmacodynamics studies (PK/PD) taking growth and maturation into account are necessary to rationalize dosing strategies in children. Currently, traditional animal models such as rats, mice, dogs and primates are used to conduct pharmacokinetic and pharmacodynamic studies, however age-related trials are rather uncommon. Moreover, these species have several shortcomings as animal models, such as a different physiology and anatomy of the gastrointestinal tract in dogs or the ethical aspects for the use of primates. In contrast, piglets might be potential biomedical pediatric animal models because of the good resemblance with humans, anatomically, physiologically and biochemically. 
This review summarizes the comparative anatomy and physiology and postnatal development of piglets and infants, focusing on six major topics, namely growth, cardiovascular system, gastrointestinal tract, liver, kidney and integument. Furthermore, the application of piglets as animal model in pediatric PK/PD research is discussed.},
  author       = {Gasthuys, Elke and Vandecasteele, Tim and De Bruyne, Pauline and Vande Walle, Johan and De Backer, Patrick and Cornillie, Pieter and Devreese, Mathias and Croubels, Siska},
  issn         = {1381-6128},
  journal      = {CURRENT PHARMACEUTICAL DESIGN},
  keyword      = {piglet.,physiology,pharmacokinetic,pediatric,ontogeny,drug design,Animal model,anatomy,BROWN ADIPOSE-TISSUE,PANCREATIC EXOCRINE SECRETION,GLOMERULAR-FILTRATION-RATE,POSTNATAL-DEVELOPMENT,SMALL-INTESTINE,BODY-COMPOSITION,DOMESTIC PIG,NEWBORN PIGLETS,RENAL-FUNCTION,HUMAN LIVER},
  language     = {eng},
  number       = {26},
  pages        = {4069--4085},
  title        = {The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmacodynamic drug testing},
  url          = {http://dx.doi.org/10.2174/1381612822666160303111031},
  volume       = {22},
  year         = {2016},
}

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