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Dhondt L, Croubels S, De Paepe P, et al. Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers. Front Pharmacol. 2020;11:883doi: 10.3389/fphar.2020.00883.
Dhondt, L., Croubels, S., De Paepe, P., Wallis, S. C., Pandey, S., Roberts, J. A., Lipman, J., De Cock, P., & Devreese, M. (2020). Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers. Frontiers in pharmacology, 11883. https://doi.org/10.3389/fphar.2020.00883
Dhondt, Laura, et al. "Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers." Frontiers in pharmacology vol. 11 (2020): 883. doi: https://doi.org/10.3389/fphar.2020.00883
Dhondt L, Croubels S, De Paepe P, Wallis SC, Pandey S, Roberts JA, Lipman J, De Cock P, Devreese M. Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers. Front Pharmacol. 2020 Jun 12;11:883. doi: 10.3389/fphar.2020.00883. eCollection 2020. PMID: 32595506; PMCID: PMC7303324.
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Front Pharmacol. 2020 Jun 12;11:883. doi: 10.3389/fphar.2020.00883. eCollection 2020.

Conventional Pig as Animal Model for Human Renal Drug Excretion Processes: Unravelling the Porcine Renal Function by Use of a Cocktail of Exogenous Markers.

Frontiers in pharmacology

Laura Dhondt, Siska Croubels, Peter De Paepe, Steven C Wallis, Saurabh Pandey, Jason A Roberts, Jeffrey Lipman, Pieter De Cock, Mathias Devreese

Affiliations

  1. Department of Pharmacology, Toxicology and Biochemistry, Ghent University, Merelbeke, Belgium.
  2. Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
  3. UQ Centre for Clinical Research, The University of Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
  4. Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
  5. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.
  6. Department of Pharmacy, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
  7. Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
  8. Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
  9. Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.

PMID: 32595506 PMCID: PMC7303324 DOI: 10.3389/fphar.2020.00883

Abstract

Over recent years, pigs have been promoted as potential animal model due to their anatomical and physiological similarities with humans. However, information about the contribution of distinct renal elimination processes [glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular secretion, and reabsorption] in pigs is currently limited. Therefore, a cocktail of renal markers, consisting of iohexol (GFR), para-aminohippuric acid (ERPF and net tubular anion secretion), pindolol (net tubular cation secretion), and fluconazole (net tubular reabsorption) was administered intravenously to 7-week-old male conventional pigs. Plasma and urinary concentrations were determined using validated analytical methods. The clearance of iohexol (GFR) was 97.87 ± 16.05 ml/min/m² (mean ± SD). The ERPF, calculated as the renal clearance of PAH, was 226.77 ± 62.45 ml/min/m², whereas the net tubular secretion of PAH was 130.28 ± 52.62 ml/min/m². The net tubular secretion of R-pindolol and S-pindolol was 13.53 ± 12.97 and 18.01 ± 39.23 ml/min/m², respectively. The net tubular reabsorption of fluconazole was 78.32 ± 13.52 ml/min/m². Overall, this cocktail of renal markers was considered to be safe for use in pigs since no adverse effects were observed. Iohexol, PAH and fluconazole were considered suitable renal marker to assess the porcine renal function. Pindolol seems less appropriate due to the high degree of nonrenal clearance in pigs. The values of GFR, ERPF, and anion secretion are within the same range for both human and pig. Regarding the tubular reabsorption of fluconazole, slightly higher values were obtained for pigs. Nevertheless, these results indicate the conventional pig could be an appropriate animal model to study renal drug elimination processes in humans.

Copyright © 2020 Dhondt, Croubels, De Paepe, Wallis, Pandey, Roberts, Lipman, De Cock and Devreese.

Keywords: animal model; fluconazole; iohexol; para-aminohippuric acid; piglet; pindolol; renal function

References

  1. Eur J Clin Microbiol Infect Dis. 1994 Apr;13(4):325-9 - PubMed
  2. Pflugers Arch. 1985 Sep;405(1):66-9 - PubMed
  3. Curr Pharm Des. 2016;22(26):4069-85 - PubMed
  4. Clin Pharmacol Ther. 1980 Nov;28(5):575-80 - PubMed
  5. Surg Clin North Am. 1975 Aug;55(4):775-86 - PubMed
  6. J Am Soc Nephrol. 2009 Nov;20(11):2305-13 - PubMed
  7. J Invest Surg. 2000 May-Jun;13(3):133-45 - PubMed
  8. Nephron. 2018;140(1):1-8 - PubMed
  9. J Pharm Sci. 1995 Mar;84(3):307-11 - PubMed
  10. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Jun 1;1117:77-85 - PubMed
  11. Acta Physiol Scand. 1970 Oct;80(2):249-53 - PubMed
  12. Toxicol Pathol. 2016 Jun;44(4):575-90 - PubMed
  13. Clin Pharmacokinet. 1989 Jan;16(1):38-54 - PubMed
  14. Crit Care. 2014 Nov 29;18(6):657 - PubMed
  15. Pediatr Nephrol. 2007 Nov;22(11):1839-48 - PubMed
  16. Kidney Int. 2001 Jan;59(1):295-303 - PubMed
  17. J Endourol. 1997 Feb;11(1):27-32 - PubMed
  18. Clin Pharmacokinet. 1993 Jan;24(1):10-27 - PubMed
  19. Scand J Clin Lab Invest. 1997 May;57(3):241-52 - PubMed
  20. J Feline Med Surg. 2001 Sep;3(3):143-7 - PubMed
  21. Br J Clin Pharmacol. 1993 Jan;35(1):20-9 - PubMed
  22. Br J Clin Pharmacol. 2001 Jun;51(6):547-55 - PubMed
  23. Pediatr Clin North Am. 2001 Dec;48(6):1425-40; vii-viii - PubMed
  24. Clin Pharmacokinet. 1998 May;34(5):375-404 - PubMed
  25. Clin Kidney J. 2016 Oct;9(5):682-99 - PubMed
  26. Br J Urol. 1995 Dec;76(6):783-9 - PubMed
  27. J Toxicol Environ Health B Crit Rev. 2009;12(5-6):440-72 - PubMed
  28. Mol Biosyst. 2011 Sep;7(9):2577-88 - PubMed
  29. Antimicrob Agents Chemother. 1985 Nov;28(5):648-53 - PubMed
  30. Int J Mol Sci. 2018 Jan 12;19(1): - PubMed
  31. Physiologist. 1985 Feb;28(1):53-63 - PubMed
  32. J Pharmacol Exp Ther. 1999 Oct;291(1):229-38 - PubMed
  33. Front Pharmacol. 2017 Jun 29;8:431 - PubMed
  34. Pharm Res. 2003 Jul;20(7):1015-21 - PubMed
  35. J Clin Invest. 1949 Sep;28(5 Pt 2):1144-62 - PubMed
  36. Am Heart J. 1982 Aug;104(2 Pt 2):357-64 - PubMed
  37. Clin Pharmacokinet. 2003;42(14):1193-211 - PubMed
  38. Chemotherapy. 1993;39(1):6-12 - PubMed
  39. Clin Cardiol. 1986 Apr;9(4):157-60 - PubMed
  40. Lab Anim. 2017 Oct;51(5):498-508 - PubMed
  41. Am J Kidney Dis. 1994 Mar;23(3):374-81 - PubMed
  42. J Clin Invest. 1985 Nov;76(5):1720-6 - PubMed
  43. Biol Neonate. 1979;35(3-4):180-7 - PubMed
  44. Vet Pathol. 2012 Mar;49(2):344-56 - PubMed
  45. Kidney Int. 1985 Jan;27(1):9-16 - PubMed
  46. Eur J Clin Pharmacol. 2009 Aug;65(8):757-73 - PubMed
  47. J Am Assoc Lab Anim Sci. 2017 Apr 25;: - PubMed
  48. Sci Rep. 2019 Jun 25;9(1):9233 - PubMed
  49. J Am Soc Nephrol. 1995 Aug;6(2):257-63 - PubMed
  50. J Pharmacol Toxicol Methods. 1999 Feb;41(1):17-25 - PubMed

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