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Animal Models for Percutaneous Absorption

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Topical Drug Bioavailability, Bioequivalence, and Penetration

Abstract

Animal models are used to predict human in vivo percutaneous absorption/penetration. Monkeys, pigs, rats, rabbits, guinea pigs, hairless rodents such as hairless rats, hairless mice, and hairless guinea pigs are among the animals most used for this purpose. Each animal model has its own advantages and weaknesses or limitations. Thus, we need to be familiar with each animal model’s characteristics as well as experimental methods and conditions to better correlate animal data with human skin absorption.

As this book was first published in 1993, we reviewed the original papers published after 1993 that described permeability of both animal and human skin. It showed that monkeys, pigs, and hairless guinea pigs are more predictive of human skin absorption/penetration and common laboratory animals, such as rats, rabbits, guinea pigs, generally overestimate human skin absorption/penetration.

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References

  1. Environmental Protection Agency (EPA). Protection for subjects in human research. Final rule. Fed Regist. 2006;71(24):6137–76.

    Google Scholar 

  2. Jakasa I, Kezic S. Evaluation of in-vivo animal and in-vitro models for prediction of dermal absorption in man. Hum Exp Toxicol. 2008;27(4):281–8. doi:10.1177/0960327107085826.

    Article  CAS  PubMed  Google Scholar 

  3. Simon GA, Maibach HI. The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations–an overview. Skin Pharmacol Appl Skin Physiol. 2000;13(5):229–34.

    Article  CAS  PubMed  Google Scholar 

  4. Bartek MJ, LaBudde JA, Maibach HI. Skin permeability in vivo: comparison in rat, rabbit, pig and man. J Invest Dermatol. 1972;58(3):114–23.

    Article  CAS  PubMed  Google Scholar 

  5. Montagna W. The skin of nonhuman primates. Am Zoologist. 1972;12:109–24.

    Google Scholar 

  6. Wester RC, Melendres J, Logan F, Hui X, Maiback HI, Wade M, Huang KC. Percutaneous absorption of 2,4-dichlorophenoxyacetic acid from soil with respect to soil load and skin contact time: in vivo absorption in rhesus monkey and in vitro absorption in human skin. J Toxicol Environ Health. 1996;47(4):335–44.

    Article  CAS  PubMed  Google Scholar 

  7. Surber C, Wilhelm KP, Maibach HI. In vivo percutaneous absorption of [14C] acitretin in the hairless guinea pig and in the rhesus monkey. Arzneimittelforschung. 1993;43(9):1001–4.

    CAS  PubMed  Google Scholar 

  8. Panchagnula R, Stemmer K, Ritschel WA. Animal models for transdermal drug delivery. Methods Find Exp Clin Pharmacol. 1997;19(5):335–41.

    CAS  PubMed  Google Scholar 

  9. Jacobi U, Kaiser M, Toll R, Mangelsdorf S, Audring H, Otberg N, Sterry W, Lademann J. Porcine ear skin: an in vitro model for human skin. Skin Res Technol. 2007;13(1):19–24.

    Article  PubMed  Google Scholar 

  10. Debeer S, Le Luduec JB, Kaiserlian D, Laurent P, Nicolas JF, Dubois B, Kanitakis J. Comparative histology and immunohistochemistry of porcine versus human skin. Eur J Dermatol. 2013;23(4):456–66.

    PubMed  Google Scholar 

  11. Boudry I, Trescos Y, Vallet V, Cruz C, Lallement G. Methods and models for percutaneous absorption studies of organophosphates. Pathol Biol (Paris). 2008;56(5):292–9. doi:10.1016/j.patbio.2007.09.024.

    Article  CAS  Google Scholar 

  12. Zendzian RP. Dermal absorption of pesticides in the rat. AIHAJ. 2000;61(4):473–83.

    Article  CAS  PubMed  Google Scholar 

  13. Barbero AM, Frasch HF. Pig and guinea pig skin as surrogates for human in vitro penetration studies: a quantitative review. Toxicol In Vitro. 2009;23(1):1–13. doi:10.1016/j.tiv.2008.10.008.

    Article  CAS  PubMed  Google Scholar 

  14. Godin B, Touitou E. Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models. Adv Drug Deliv Rev. 2007;59(11):1152–61.

    Article  CAS  PubMed  Google Scholar 

  15. Capt A, Luzy AP, Esdaile D, Blanck O. Comparison of the human skin grafted onto nude mouse model with in vivo and in vitro models in the prediction of percutaneous penetration of three lipophilic pesticides. Regul Toxicol Pharmacol. 2007;47(3):274–87.

    Article  CAS  PubMed  Google Scholar 

  16. van Ravenzwaay B, Leibold E. The significance of in vitro rat skin absorption studies to human risk assessment. Toxicol In Vitro. 2004;18(2):219–25.

    Article  PubMed  Google Scholar 

  17. van Ravenzwaay B, Leibold E. A comparison between in vitro rat and human and in vivo rat skin absorption studies. Hum Exp Toxicol. 2004;23(9):421–30.

    Article  PubMed  Google Scholar 

  18. US Environmental Protection Agency. Dermal exposure assessment: principles and applications. EPA/600/8–91/011B. Washington, DC: U.S. EPA, Office of Health and Environmental Assessment; 1992.

    Google Scholar 

  19. Thongsinthusak T, Ross J, Meinders D. Guidance for the preparation of human pesticide exposure assessment documents. Report No. HS-1612. Workers Health & Safety Branch, Department of Pesticide Regulation, California Environmental Protection Agency, Sacramento, CA; 2003.

    Google Scholar 

  20. World Health Organization, International Programme on Chemical Safety. Dermal absorption. Environmental health criteria 235. Geneva: WHO Press; 2005.

    Google Scholar 

  21. Ross JH, Reifenrath WG, Driver JH. Estimation of the percutaneous absorption of permethrin in humans using the parallelogram method. J Toxicol Environ Health A. 2011;74(6):351–63. doi:10.1080/15287394.2011.534425.

    Article  CAS  PubMed  Google Scholar 

  22. Nicoli S, Padula C, Aversa V, Vietti B, Wertz PW, Millet A, Falson F, Govoni P, Santi P. Characterization of rabbit ear skin as a skin model for in vitro transdermal permeation experiments: histology, lipid composition and permeability. Skin Pharmacol Physiol. 2008;21(4):218–26. doi:10.1159/000135638.

    Article  CAS  PubMed  Google Scholar 

  23. Nicoli S, Cappellazzi M, Colombo P, Santi P. Characterization of the permselective properties of rabbit skin during transdermal iontophoresis. J Pharm Sci. 2003;92(7):1482–8.

    Article  CAS  PubMed  Google Scholar 

  24. Shah VP, Flynn GL, Guy RH, Maibach HI, Schaefer H, Skelly JP, Wester RC, Yacobi A. Workshop report on in vivo percutaneous penetration/absorption. Washington DC, 1989. Skin Pharmacol. 1991;4(3):220–8.

    Article  PubMed  Google Scholar 

  25. Chantasart D, Li SK, He N, Warner KS, Prakongpan S, Higuchi WI. Mechanistic studies of branched-chain alkanols as skin permeation enhancers. J Pharm Sci. 2004;93(3):762–79.

    Article  CAS  PubMed  Google Scholar 

  26. Simon GA, Maibach HI. Relevance of hairless mouse as an experimental model of percutaneous penetration in man. Skin Pharmacol Appl Skin Physiol. 1998;11(2):80–6.

    Article  CAS  PubMed  Google Scholar 

  27. Sueki H, Gammal C, Kudoh K, Kligman AM. Hairless guinea pig skin: anatomical basis for studies of cutaneous biology. Eur J Dermatol. 2000;10(5):357–64.

    CAS  PubMed  Google Scholar 

  28. Frasch HF, Barbero AM. A paired comparison between human skin and hairless guinea pig skin in vitro permeability and lag time measurements for 6 industrial chemicals. Cutan Ocul Toxicol. 2009;28(3):107–13. doi:10.1080/15569520902950474.

    Article  CAS  PubMed  Google Scholar 

  29. van de Sandt JJ, Meuling WJ, Elliott GR, Cnubben NH, Hakkert BC. Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur. Toxicol Sci. 2000;58(1):15–22.

    Article  PubMed  Google Scholar 

  30. Cnubben NH, Elliott GR, Hakkert BC, Meuling WJ, van de Sandt JJ. Comparative in vitro–in vivo percutaneous penetration of the fungicide ortho-phenylphenol. Regul Toxicol Pharmacol. 2002; 35(2 Pt 1):198–208.

    Article  CAS  PubMed  Google Scholar 

  31. Riviere JE, Bowman KF, Monteiro-Riviere NA, Dix LP, Carver MP. The isolated perfused porcine skin flap (IPPSF). I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies. Fundam Appl Toxicol. 1986;7(3):444–53.

    Article  CAS  PubMed  Google Scholar 

  32. Wester RC, Melendres J, Sedik L, Maibach H, Riviere JE. Percutaneous absorption of salicylic acid, theophylline, 2,4-dimethylamine, diethyl hexyl phthalic acid, and p-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicol Appl Pharmacol. 1998;151(1):159–65.

    Article  CAS  PubMed  Google Scholar 

  33. de Lange J, van Eck P, Bruijnzeel PL, Elliott GR. The rate of percutaneous permeation of xylene, measured using the “perfused pig ear” model, is dependent on the effective protein concentration in the perfusing medium. Toxicol Appl Pharmacol. 1994;127(2):298–305.

    Article  CAS  PubMed  Google Scholar 

  34. Wagner SM, Nogueira AC, Paul M, Heydeck D, Klug S, Christ B. The isolated normothermic hemoperfused porcine forelimb as a test system for transdermal absorption studies. J Artif Organs. 2003;6(3):183–91.

    Article  CAS  PubMed  Google Scholar 

  35. Heidemann R, Menke G, Letzel H, Rietbrock N. Serum concentration of glyceryl trinitrate (GTN) in transdermal application of GTN dressings of various origins. Dtsch Med Wochenschr. 1985;110(41):1568–72.

    Article  CAS  PubMed  Google Scholar 

  36. Muller P, Imhof PR, Burkart F, Chu LC, Gerardin A. Human pharmacological studies of a new transdermal m containing nitroglycerin. Eur J Clin Pharmacol. 1982;22(6):473–80.

    Article  CAS  PubMed  Google Scholar 

  37. Eros G, Hartmann P, Berkó S, Csizmazia E, Csányi E, Sztojkov-Ivanov A, Németh I, Szabó-Révész P, Zupkó I, Kemény L. A novel murine model for the in vivo study of transdermal drug penetration. ScientificWorldJournal. 2012;2012:543536. doi:10.1100/2012/543536.

    Article  Google Scholar 

  38. Iervolino M, Cappello B, Raghavan SL, Hadgraft J. Penetration enhancement of ibuprofen from supersaturated solutions through human skin. Int J Pharm. 2001;212(1):131–41.

    Article  CAS  PubMed  Google Scholar 

  39. Swart H, Breytenbach JC, Hadgraft J, du Plessis J. Synthesis and transdermal penetration of NSAID glycoside esters. Int J Pharm. 2005;301(1–2):71–9.

    Article  CAS  PubMed  Google Scholar 

  40. Netzlaff F, Schaefer UF, Lehr CM, Meiers P, Stahl J, Kietzmann M, Niedorf F. Comparison of bovine udder skin with human and porcine skin in percutaneous permeation experiments. Altern Lab Anim. 2006;34(5):499–513.

    CAS  PubMed  Google Scholar 

  41. Reifenrath WG, Chellquist EM, Shipwash EA, Jederberg WW, Krueger GG. Percutaneous penetration in the hairless dog, weanling pig and grafted athymic nude mouse: evaluation of models for predicting skin penetration in man. Br. J. Dermatol. 1984;111(Suppl. 27):123–35.

    Article  CAS  PubMed  Google Scholar 

  42. Maibach HI, Feldman RJ, Milby TH, Serat WF. Regional variation in percutaneous penetration in man. Pesticides. Arch Environ Health. 1971;23(3):208–11.

    Article  CAS  PubMed  Google Scholar 

  43. Feldmann RJ, Maibach HI. Percutaneous penetration of some pesticides and herbicides in man. Toxicol Appl Pharmacol. 1974;28(1):126–32.

    Article  CAS  PubMed  Google Scholar 

  44. Woollen BH, Marsh JR, Laird WJ, Lesser JE. The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration. Xenobiotica. 1992;22(8):983–91.

    Article  CAS  PubMed  Google Scholar 

  45. Wester RC, Maibach HI. Relationship of topical dose and percutaneous absorption in rhesus monkey and man. J Invest Dermatol. 1976;67(4):518–20.

    Article  CAS  PubMed  Google Scholar 

  46. Dupuis D, Rougier A, Roguet R, Lotte C, Kalopissis G. In vivo relationship between horny layer reservoir effect and percutaneous absorption in human and rat. J Invest Dermatol. 1984;82(4):353–6.

    Article  CAS  PubMed  Google Scholar 

  47. Wester RC, Noonan PK, Maibach HI. Variations in percutaneous absorption of testosterone in the rhesus monkey due to anatomic site of application and frequency of application. Arch Dermatol Res. 1980;267(3):229–35.

    Article  CAS  PubMed  Google Scholar 

  48. Ngo M, Maibach HI. 15 Principles of percutaneous penetration. In: Parameters for Pesticide QSAR and PBPK/PD Models for Human Risk Assessment, ACS Symposium Series, Vol. 1099, Washington DC: American Chemical Society; 2012. pp. 67–86. doi:10.1021/bk-2012-1099.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Dermatology, University of California, 90 Medical Center Way, Surge 110, 94143-0989, San Francisco, CA, USA

    Eui Chang Jung MD, PhD

  2. Department of Dermatology, School of Medicine, University of California, San Francisco, CA, USA

    Howard I. Maibach MD

Authors
  1. Eui Chang Jung MD, PhD
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  2. Howard I. Maibach MD
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Corresponding author

Correspondence to Eui Chang Jung MD, PhD .

Editor information

Editors and Affiliations

  1. Pharmaceutical Consultant, North Potomac, Maryland, USA

    Vinod P. Shah

  2. University of California, San Francisco School of Medicine, Department of Dermatology, San Francisco, California, USA

    Howard I. Maibach

  3. The Defence Science and Technology Laboratory, Biomedical Sciences Department, Salisbury, United Kingdom

    John Jenner

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Jung, E., Maibach, H. (2014). Animal Models for Percutaneous Absorption. In: Shah, V., Maibach, H., Jenner, J. (eds) Topical Drug Bioavailability, Bioequivalence, and Penetration. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1289-6_2

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