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Tissue distribution and dermal drug determination of indomethacin transdermal-absorption patches

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Abstract

The tissue distribution and percutaneous drug absorption of indomethacin (IND) patches were studied using commercial IND as a comparison. The concentration of IND in skin, plasma, and muscle in mice was measured by LC-MS/MS, and the IND concentration in the dermis of rats was also monitored by microdialysis. After percutaneous administration, the “double-peak” phenomenon occurred in different tissues, and the IND concentration was ranked as skin first, followed by plasma and then muscle. In particular, skin acted as a reservoir for drug release, and the “secondary hump” in tissue distribution was attributed to the subsequent release of lipophilic IND in skin. It was concluded that examination of the tissue distribution and application of a microdialysis technique provided an effective means of evaluating indomethacin pharmacokinetics.

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References

  1. Sagar V, Ahamed RN. Gastric mucosal cellular changes induced by indomethacin (NSAID) in male albino rats. Indian J Exp Biol. 1999;37(4):365–9.

    CAS  PubMed  Google Scholar 

  2. Xie G, Zhou D, Cheng K-W, Wong CC, Rigas B. Comparative in vitro metabolism of phospho-tyrosol-indomethacin by mice, rats and humans. Biochem Pharmacol. 2013;85(8):1195–202. doi:10.1016/j.bcp.2013.01.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Arroyo-Lira AG, Rodríguez-Ramos F, Chávez-Piña AE. Synergistic antinociceptive effect and gastric safety of the combination of docosahexaenoic acid and indomethacin in rats. Pharmacol Biochem Behav. 2014;122:74–81. doi:10.1016/j.pbb.2014.03.015.

    Article  CAS  PubMed  Google Scholar 

  4. Abioye AO, Issah S, Kola-Mustapha AT. Ex vivo skin permeation and retention studies on chitosan-ibuprofen-gellan ternary nanogel prepared by in situ ionic gelation technique-a tool for controlled transdermal delivery of ibuprofen. Int J Pharm. 2015;490(1–2):112–30. doi:10.1016/j.ijpharm.2015.05.030.

    Article  CAS  PubMed  Google Scholar 

  5. Tan HS, Pfister WR. Pressure-sensitive adhesives for transdermal drug delivery systems. Pharm Sci Technol Today. 1999;2(2):60–9. doi:10.1016/S1461-5347(99)00119-4.

    Article  CAS  PubMed  Google Scholar 

  6. Lee KE, Choi YJ, Oh BR, Chun IK, Gwak HS. Formulation and in vitro/in vivo evaluation of levodopa transdermal delivery systems. Int J Pharm. 2013;456(2):432–6. doi:10.1016/j.ijpharm.2013.08.044.

    Article  CAS  PubMed  Google Scholar 

  7. Morrow JD, Hill KE, Burk RF, Nammour TM, Bade KF, et al. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990;87:9383–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Olugemo K, Solorio D, Sheridan C, Young CL. Pharmacokinetics and safety of low dose submicron indomethacin 20 and 40 mg compared with indomethacin 50 mg. Postgrad Med. 2015:223–31. doi:10.1080/00325481.2015.1000231.

  9. De Castro WV, Marchand S, Lamarche I, Couet W. Effect of experimentally induced hypovolemia on ertapenem tissue distribution using microdialysis in rats. Eur J Pharm Sci. 2014;51:45–50. doi:10.1016/j.ejps.2013.08.017.

    Article  CAS  PubMed  Google Scholar 

  10. Konings I, Engels FK, Sleijfer S, Verweij J, Wiemer EAC, Loos WJ. Application of prolonged microdialysis sampling in carboplatin-treated cancer patients. Cancer Chemother Pharmacol. 2009;64(3):509–16. doi:10.1007/s00280-008-0898-0.

    Article  CAS  PubMed  Google Scholar 

  11. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001;14(2):101–14. doi:10.1016/s0928-0987(01)00167-1.

    Article  CAS  PubMed  Google Scholar 

  12. Potts R, Guy R. Predicting skin permeability. Pharm Res. 1992;9(5):663–9. doi:10.1023/A:1015810312465.

    Article  CAS  PubMed  Google Scholar 

  13. Murphy NP. Dynamic measurement of extracellular opioid activity: status quo, challenges, and significance in rewarded behaviors. ACS Chem Neurosci. 2015;6(1):94–107. doi:10.1021/cn500295q.

    Article  CAS  PubMed  Google Scholar 

  14. Plock N, Kloft C. Microdialysis—theoretical background and recent implementation in applied life sciences. Eur J Pharm Sci. 2005;25(1):1–24. doi:10.1016/j.ejps.2005.01.017.

    Article  CAS  PubMed  Google Scholar 

  15. Tettey-Amlalo RNO, Kanfer I, Skinner MF, Benfeldt E, Verbeeck RK. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel. Eur J Pharm Sci. 2009;36(2–3):219–25. doi:10.1016/j.ejps.2008.09.002.

    Article  CAS  PubMed  Google Scholar 

  16. Brill MJE, Houwink API, Schmidt S, Van Dongen EPA, Hazebroek EJ, van Ramshorst B, et al. Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. J Antimicrob Chemother. 2014;69(3):715–23. doi:10.1093/jac/dkt444.

    Article  CAS  PubMed  Google Scholar 

  17. Bungay PM, Morrison PF, Dedrick RL. Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro. Life Sci. 1990;46(2):105–19.

    Article  CAS  PubMed  Google Scholar 

  18. Schnetz E, Fartasch M. Microdialysis for the evaluation of penetration through the human skin barrier—a promising tool for future research? Eur J Pharm Sci. 2001;12(3):165–74. doi:10.1016/s0928-0987(00)00155-x.

    Article  CAS  PubMed  Google Scholar 

  19. Chaurasia CS. In vivo microdialysis sampling: theory and applications. Biomed Chromatogr. 1999;13(5):317–32. doi:10.1002/(sici)1099-0801(199908)13:5<317::aid-bmc891>3.0.co;2-i.

    Article  CAS  PubMed  Google Scholar 

  20. Couto A, Fernandes R, Cordeiro MNS, Reis SS, Ribeiro RT, Pessoa AM. Dermic diffusion and stratum corneum: a state of the art review of mathematical models. J Control Release. 2014;177:74–83. doi:10.1016/j.jconrel.2013.12.005.

    Article  CAS  PubMed  Google Scholar 

  21. Chen J, Wang XM, Wang J, Liu GL, Tang X. Evaluation of brain-targeting for the nasal delivery of ergoloid mesylate by the microdialysis method in rats. Eur J Pharm Biopharm. 2008;68(3):694–700. doi:10.1016/j.ejpb.2007.08.013.

    Article  CAS  PubMed  Google Scholar 

  22. Azeredo FJ, Dalla Costa T, Derendorf H. Role of microdialysis in pharmacokinetics and pharmacodynamics: current status and future directions. Clin Pharmacokinet. 2014;53(3):205–12. doi:10.1007/s40262-014-0131-8.

    Article  CAS  PubMed  Google Scholar 

  23. Sinnollareddy MG, Roberts MS, Lipman J, Peake SL, Roberts JA. Influence of sustained low-efficiency diafiltration (SLED-f) on interstitial fluid concentrations of fluconazole in a critically ill patient: use of microdialysis. Int J Antimicrob Agents. 2015;46(1):121–4. doi:10.1016/j.ijantimicag.2015.02.017.

    Article  CAS  PubMed  Google Scholar 

  24. Kreilgaard M. Assessment of cutaneous drug delivery using microdialysis. Adv Drug Deliv Rev. 2002;54:S99–S121. doi:10.1016/s0169-409x(02)00117-5.

    Article  CAS  PubMed  Google Scholar 

  25. Ding P, Xu H, Wei G, Zheng J. Microdialysis sampling coupled to HPLC for transdermal delivery study of ondansetron hydrochloride in rats. Biomed Chromatogr. 2000;14(3):141–3. doi:10.1002/1099-0801(200005)14:3<141::aid-bmc937>3.3.co;2-q.

    Article  CAS  PubMed  Google Scholar 

  26. Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol. 2015;27(6):269–80. doi:10.1093/intimm/dxv013.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge financial support from the National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No. 2014ZX09507001-009) and the Science and Technology Research Project of Education Department of Liaoning Province (L2013390).

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Authors and Affiliations

  1. Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China

    Jingjing Ma, Ying Gao, Yinghua Sun, Dawei Ding, Qi Zhang, Bingjun Sun, Menglin Wang, Jin Sun & Zhonggui He

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  1. Jingjing Ma
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  2. Ying Gao
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  8. Jin Sun
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Correspondence to Yinghua Sun.

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Ma, J., Gao, Y., Sun, Y. et al. Tissue distribution and dermal drug determination of indomethacin transdermal-absorption patches. Drug Deliv. and Transl. Res. 7, 617–624 (2017). https://doi.org/10.1007/s13346-017-0392-5

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