Cutaneous metabolism and active transport in transdermal drug delivery

Toxicology of the Skin

Volumn , Issue , 2010, Pages 69-82

  Dancik, Yuri ^a   Thompson, Camilla ^b   Krishnan, Gayathri ^c   Roberts, Michael S ^a,b  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^c CURTIN UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 79957689849     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (77)

1. Madison KC. Barrier function of the skin: “La Raison d’Etre” of the epidermis. J Invest Dermatol 2003; 121(2):231-241.
2. Guy RH, Hadgraft J, Bucks DA. Transdermal drug delivery and cutaneous metabolism. Xenobiotica 1987; 17(3):325-343.
3. Krien PM, Kermici M. Evidence for the existence of a self-regulated enzymatic process within the human stratum corneum-an unexpected role for urocanic acid. J Invest Dermatol 2000; 115(3):414-420.
4. Forestier JP. Les enzymes de l′′espace extra-cellulaire du stratum corneum. Int J Cosmet Sci 1992; 14(2):47-63.
5. Oesch F, Fabian E, Oesch-Bartlomowicz B, et al. Drug-metabolizing enzymes in the skin of man, rat, and pig. Drug Metab Rev 2007; 39(4):659-698.
6. Afaq F, Mukhtar H. Effects of solar radiation on cutaneous detoxification pathways. J Photochem Photobiol B 2001; 63(1-3):61-69.
7. Ahmad N, Mukhtar H. Cytochrome p450: a target for drug development for skin diseases. J Invest Dermatol 2004; 123(3):417-425.
8. Bucks DAW. Skin Structure and Metabolism—Relevance to the design of cutaneous therapeutics. Pharm Res 1984(4):148-153.
9. Ziboh VA, Miller CC, Cho YH. Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites. Am J Clin Nutr 2000; 71(1):361s-366s.
10. Horrobin DF. Essential fatty acid metabolism and its modification in atopic eczema. Am J Clin Nutr 2000; 71(1):367s-372s.
11. Sies H, Stahl W. Nutritional protection against skin damage from sunlight. Annu Rev Nutr 2004; 24:173-200.
12. Pavek P, Dvorak Z. Xenobiotic-induced transcriptional regulation of xenobiotic metabolizing enzymes of the cytochrome P450 superfamily in human extrahepatic tissues. Curr Drug Metab 2008; 9(2):129-143.
13. Merk HF, Baron JM, Neis MM, et al. Skin: major target organ of allergic reactions to small molecular weight compounds. Toxicol Appl Pharmacol 2007; 224(3):313-317.
14. Du L, Hoffman SM, Keeney DS. Epidermal CYP2 family cytochromes P450. Toxicol Appl Pharmacol 2004; 195(3):278-287.
15. Lockley DJ, Howes D, Williams FM. Cutaneous metabolism of glycol ethers. Arch Toxicol 2005; 79(3):160-168.
16. Janmohamed A, Dolphin CT, Phillips IR, et al. Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450. Biochem Pharmacol 2001; 62(6):777-786.
17. Kawakubo Y, Merk HF, Masaoudi TA, et al. N-Acetylation of paraphenylenediamine in human skin and keratinocytes. J Pharmacol Exp Ther 2000; 292(1):150-155.
18. Liu P, Higuchi WI, Song WQ, et al. Quantitative evaluation of ethanol effects on diffusion and metabolism of beta-estradiol in hairless mouse skin. Pharm Res 1991; 8(7):865-872.
19. Hikima T, Yamada K, Kimura T, et al. Comparison of skin distribution of hydrolytic activity for bioconversion of beta-estradiol 17-acetate between man and several animals in vitro. Eur J Pharm Biopharm 2002; 54(2):155-160.
20. Wilkinson SC, Williams FM. Cutaneous Metabolism, in Dermal Absorption and Toxicity Assessment. In: Roberts MS, Walters KA, eds. New York: Informa Healthcare, 2008:89-115.
21. Dancik Y, Jepps OG, Roberts MS. Physiologically Based Pharmacokinetics of and Pharmacodynamics of Skin, in Dermal Absorption and Toxicity Assessment. In: Roberts MS, Walters KA, eds. New York: Informa Healthcare, 2008:179-207.
22. Kao J, Hall J. Skin absorption and cutaneous first pass metabolism of topical steroids: in vitro studies with mouse skin in organ culture. J Pharmacol Exp Ther 1987; 241(2):482-487.
23. Imhof PR, Vuillemin T, Gérardin A, et al. Studies of the bioavailability of nitroglycerin from a transdermal therapeutic system (Nitroderm Tts). Eur J Clin Pharmacol 1984; 27(1):7-12.
24. Ito K, Nguyen HT, Kato Y, et al. P-Glycoprotein (Abcb1) is involved in absorptive drug transport in skin. J Control Release 2008; 131(3):198-204.
25. Bleasby K, Castle JC, Roberts CJ, et al. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica 2006; 36(10-11):963-988.
26. Schuessler M, Astecker N, Herzig G, et al. Skin is an autonomous organ in synthesis, two-step activation and degradation of vitamin D-3: CYP27 in epidermis completes the set of essential vitamin D-3-hydroxylases. Steroids 2001; 66(3-5):399-408.
27. Lehmann B, Querings K, Reichrath J. Vitamin D and skin: new aspects for dermatology. Exp Dermatol 2004; 13:11-15.
28. Lehmann B, Genehr T, Knuschke P, et al. UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D-3 in an in vitro human skin equivalent model. J Invest Dermatol 2001; 117(5):1179-1185.
29. Smith G, Wolf CR, Deeni YY, et al. Cutaneous expression of cytochrome P450CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases. Lancet 2003; 361(9366):1336-1343.
30. Smith G, Ibbotson SH, Comrie MM, et al. Regulation of cutaneous drug-metabolizing enzymes and cytoprotective gene expression by topical drugs in human skin in vivo. Br J Dermatol 2006; 155(2):275-281.
31. Duell EA, Aström A, Griffiths CE, et al. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptormediated transcription in vitro. J Clin Invest 1992; 90(4):1269-1274.
32. Rolsted K, Benfeldt E, Kissmeyer AM, et al. Cutaneous in vivo Metabolism of Topical Lidocaine Formulation in Human Skin. Skin Pharmacol Physiol 2009; 22(3):124-127.
33. Ng KM, Chu I, Bronaugh RL, et al. Percutaneous absorption and metabolism of pyrene, benzo[a]pyrene, and di(2-ethylhexyl) phthalate: comparison of in vitro and in vivo results in the hairless guinea pig. Toxicol Appl Pharmacol 1992; 115(2): 216-223.
34. Shimizu Y, Nakatsuru Y, Ichinose M, et al. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A 2000; 97(2): 779-782.
35. Qiao GL, Riviere JE. Systemic uptake and cutaneous disposition of pentachlorophenol in a sequential exposure scenario: effects of skin preexposure to benzo [a]pyrene. J Toxicol Environ Health A 2002; 65(18):1307-1331.
36. Lobemeier C, Tschoetschel C, Westie S, et al. Hydrolysis of parabenes by extracts from differing layers of human skin. Biol Chem 1996; 377(10):647-651.
37. Prusakiewicz JJ, Harville HM, Zhang Y, et al. Parabens inhibit human skin estrogen sulfotransferase activity: Possible link to paraben estrogenic effects. Toxicology 2007; 232(3):248-256.
38. Boogaard PJ, van Elburg PA, de Kloe KP, et al. Metabolic inactivation of 2-oxiranylmethyl 2-ethyl-2,5-dimethylhexanoate (C(10)GE) in skin, lung and liver of human, rat and mouse. Xenobiotica 1999; 29(10):987-1006.
39. Smith CK, Moore CA, Elahi EN, et al. Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol. Toxicol Appl Pharmacol 2000; 168(3):189-199.
40. Cheung C, Hotchkiss SA, Pease CK. Cinnamic compound metabolism in human skin and the role metabolism may play in determining relative sensitisation potency. J Dermatol Sci 2003; 31(1):9-19.
41. Lockley DJ, Howes D, Williams FM. Percutaneous penetration and metabolism of 2-ethoxyethanol. Toxicol Appl Pharmacol 2002; 180(2):74-82.
42. Lockley DJ, Howes D, Williams FM. Percutaneous penetration and metabolism of 2-butoxyethanol. Arch Toxicol 2004; 78(11):617-628.
43. Meyer UA. Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm 1996; 24(5):449-459.
44. Gysler A, Kleuser B, Sippl W, et al. Skin penetration and metabolism of topical glucocorticoids in reconstructed epidermis and in excised human skin. Pharm Res 1999; 16(9):1386-1391.
45. Lombardi Borgia S, Schlupp P, Mehnert W, et al. In vitro skin absorption and drug release—a comparison of six commercial prednicarbate preparations for topical use. Eur J Pharm Biopharm 2008; 68(2):380-389.
46. Stinchcomb AL, Swaan PW, Ekabo O, et al. Straight-chain naltrexone ester prodrugs: diffusion and concurrent esterase biotransformation in human skin. J Pharm Sci 2002; 91(12):2571-2578.
47. Valiveti S, Paudel KS, Hammell DC, et al. In vitro/in vivo correlation of transdermal naltrexone prodrugs in hairless guinea pigs. Pharm Res 2005; 22(6):981-989.
48. Sung KC, Fang JY, Hu OY. Delivery of nalbuphine and its prodrugs across skin by passive diffusion and iontophoresis. J Control Release 2000; 67(1):1-8.
49. Morris AP, Brain KR, Heard CM. Skin permeation and ex vivo skin metabolism of O-acyl haloperidol ester prodrugs. Int J Pharm 2009; 367(1-2):44-50.
50. Mavon A, Raufast V, Redoules D. Skin absorption and metabolism of a new vitamin E prodrug, delta-tocopherol-glucoside: in vitro evaluation in human skin models. J Control Release 2004; 100(2):221-231.
51. Redoules D, Perie J, Viodé C, et al. Slow internal release of bioactive compounds under the effect of skin enzymes. J Invest Dermatol 2005; 125(2):270-277.
52. Beall HD, Sloan KB. Topical delivery of 5-fluorouracil (5-FU) by 1,3-bisalkylcarbonyl-5-FU prodrugs. Int J Pharm 2002; 231(1):43-49.
53. Doh HJ, Cho WJ, Yong CS, et al. Synthesis and evaluation of Ketorolac ester prodrugs for transdermal delivery. J Pharm Sci 2003; 92(5):1008-1017.
54. Bodor N, Buchwald P. Soft drug design: General principles and recent applications. Med Res Rev 2000; 20(1):58-101.
55. Schnorr O, Suschek CV, Kolb-Bachofen V. The importance of cationic amino acid transporter expression in human skin. J Invest Dermatol 2003; 120(6):1016-1022.
56. Schmuth M, Ortegon AM, Mao-Qiang M, et al. Differential expression of fatty acid transport proteins in epidermis and skin appendages. J Invest Dermatol 2005; 125(6): 1174-1181.
57. Schuerer NY. Implementation of fatty acid carriers to skin irritation and the epidermal barrier. Contact Dermatitis 2002; 47(4):199-205.
58. Randolph GJ, Beaulieu S, Pope M, et al. A physiologic function for p-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc Natl Acad Sci U S A 1998; 95(12):6924-6929.
59. Smith G, Dawe RS, Clark C, et al. Quantitative real-time reverse transcriptionpolymerase chain reaction analysis of drug metabolizing and cytoprotective genes in psoriasis and regulation by ultraviolet radiation. J Invest Dermatol 2003; 121(2): 390-398.
60. Li Q, Kato Y, Sai Y, et al. Multidrug resistance-associated protein 1 functions as an efflux pump of xenobiotics in the skin. Pharm Res 2005; 22(6):842-846.
61. Baron JM, Höller D, Schiffer R, et al. Expression of multiple cytochrome p450 enzymes and multidrug resistance-associated transport proteins in human skin keratinocytes. J Invest Dermatol 2001; 116(4):541-548.
62. Zeng H, Chen ZS, Belinsky MG, et al. Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res 2001; 61(19):7225-7232.
63. Keppler D, Leier I, Jedlitschky G. Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2. Biol Chem 1997; 378 (8):787-791.
64. Sprecher E, Bergman R, Sprecher H, et al. Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin. Arch Dermatol Res 1998; 290(12):656-660.
65. Schiffer R, Neis M, Höller D, et al. Active influx transport is mediated by members of the organic anion transporting polypeptide family in human epidermal keratinocytes. J Invest Dermatol 2003; 120(2):285-291.
66. Li Q, Tsuji H, Kato Y, et al. Characterization of the transdermal transport of flurbiprofen and indomethacin. J Control Release 2006; 110(3):542-556.
67. Ito K, Kato Y, Tsuji H, et al. Involvement of organic anion transport system in transdermal absorption of flurbiprofen. J Control Release 2007; 124(1-2):60-68.
68. Hopper-Borge E, Chen ZS, Shchaveleva I, et al. Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): Resistance to docetaxel. Cancer Res 2004; 64(14):4927-4930.
69. Boury-Jamot M, Sougrat R, Tailhardat M, et al. Expression and function of aquaporins in human skin: Is aquaporin-3 just a glycerol transporter? Biochim Biophys Acta 2006; 1758(8):1034-1042.
70. Baron JM, Goh LB, Yao D, et al. Modulation of P450 CYP3A4-dependent metabolism by P-glycoprotein: implications for P450 phenotyping. J Pharmacol Exp Ther 2001; 296(2):351-358.
71. Rybczynska M, Liu R, Lu P, et al. MDR1 causes resistance to the antitumour drug miltefosine. Br J Cancer 2001; 84(10):1405-1411.
72. Eckford PD, Sharom FJ. P-glycoprotein (ABCB1) interacts directly with lipid-based anti-cancer drugs and platelet-activating factors. Biochem Cell Biol 2006; 84(6): 1022-1033.
73. Ando HY, Ho NF, Higuchi WI. Skin as an active metabolizing barrier I: Theoretical analysis of topical bioavailability. J Pharm Sci 1977; 66(11):1525-1528.
74. Bando H, Mohri S, Yamashita F, et al. Effects of skin metabolism on percutaneous penetration of lipophilic drugs. J Pharm Sci 1997; 86(6):759-761.
75. Bando H, et al. Analysis of in vitro skin penetration of acyclovir prodrugs based on a diffusion model with a metabolic process. Int J Pharm 1996; 135(1-2):91-102.
76. Boderke P, Schittkowski K, Wolf M, et al. Modeling of diffusion and concurrent metabolism in cutaneous tissue. J Theor Biol 2000; 204(3):393-407.
77. Sugibayashi K, Hayashi T, Morimoto Y. Simultaneous transport and metabolism of ethyl nicotinate in hairless rat skin after its topical application: the effect of enzyme distribution in skin. J Control Release 1999; 62(1-2):201-208.