Percutaneous absorption of steroids: Relative contributions of epidermal penetration and dermal clearance

  • O. Siddiqui
  • M. S. Roberts
  • A. E. Polack


The permeation of triamcinolone, hydrocortisone, prednisolone, corticosterone, triamdnolone acetonide, testosterone, and betamethasone-17-valerate through excised human stratum corneum was quantified. The time course of permeation could be adequately described by a simple diffusion model suggesting that shunt transport may not be important. The disappearance of these steroids from aqueous solutions applied to human and rat dermis was also monitored. The concentrations of unbound steroid in the viable epidermis appeared to be mainly related to the blood perfusion rate in the dermis and, more importantly, to the lipophilicity of the steroid. The most lipophilic steroids penetrated the human epidermis at the fastest rates but are cleared from the viable epidermis at rates comparable to those found for more polar steroids.

Key words

steroids epidermal penetration dermal clearance shunt transport dermal transport 




Intercept for fraction remaining (or area)


Intercept for fraction remaining (= 1−A)


Concentration in vehicle


Steady state concentration




Diffusion coefficient




Steady state flux (=kpCv)


Partition coefficient between stratum corneum and vehicle


Pseudo-first-order rate constant for dermal disappearance


Permeability coefficient (=KD/h)


Cumulative amount


Mean residence time


Integer value




Lag time


Partition coefficient between dermis and the aqueous solution


Rate of input


Donor volume


Volume of distribution in dermis


Volume of distribution at steady state


Percentage coefficient of variation (SD×100/mean)





Epidermis (intracellular/intercellular)




Sum of epidermal and dermal contributions


Fast rate constant for dermal disappearance


Slow rate constant for dermal disappearance


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  1. 1.
    R. J. Scheuplein, I. H. Blank, G. J. Brauner, and D. J. Macfarlane. Percutaneous absorption of steroids.J. Invest. Dermatol. 52:63–70 (1969).PubMedGoogle Scholar
  2. 2.
    I. H. Blank and R. J. Scheuplein. Transport into and within the skin.Br. J. Dermatol.,81 (Suppl 4):4–10 (1969).CrossRefGoogle Scholar
  3. 3.
    M. S. Roberts and R. A. Anderson. The percutaneous absorption of phenolic compounds: the effect of vehicles on the penetration of phenol.J. Pharm. Pharmacol. 27:599–605 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    H. Schaefer, A. Zesch, and G. Stuttgen.Skin Permeability, Springer Verlag, New York, 1982.CrossRefGoogle Scholar
  5. 5.
    J. Crank.The Mathematics of Diffusion 2nd ed., chaps. 1, 2, and 4, Clarendon Press, Oxford, 1975.Google Scholar
  6. 6.
    R. J. Scheuplein. Skin permeation.J. Physiol. Pathophysiol. 5 (Chap. 55), 1978, pp. 1693–1730.Google Scholar
  7. 7.
    B. W. Barry. Dermatological formulations. Percutaneous absorption. InDrugs and the Pharmaceutical Sciences, Vol. 18, Marcel Dekker, New York, 1983.Google Scholar
  8. 8.
    R. H. Levy and M. Rowland. Absorption kinetics of a series of local anaesthetics from rat subcutaneous tissue I.J. Pharmacokin. Biopharm. 2:313–335 (1974).CrossRefGoogle Scholar
  9. 9.
    M. S. Roberts, W. A. Favretto, A. Meyer, M. Reckmann, and T. Wongseelashote. Topical bioavailability of methyl salicylate.Aust. N. Z. J. Med. 12:303–305 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    K. Kuhota and T. Ishizaki. A theoretical consideration of percutaneous drug absorption.J. Pharmacokin. Biopharm. 13:55–72 (1985).CrossRefGoogle Scholar
  11. 11.
    R. H. Guy and J. Hadgraft. Physicochemical interpretation of the pharmacokinetics of percutaneous absorption.J. Pharmacokin. Biopharm. 11:189–203 (1983).CrossRefGoogle Scholar
  12. 12.
    W. J. Albery, R. H. Guy, and J. Hadgraft. Percutaneous absorption: Transport in the dermis.Int. J. Pharm. 15:125–148 (1983).CrossRefGoogle Scholar
  13. 13.
    K. Yamaoka, T. Nakagawa, and T. Uno. Statistical moments in pharmacokinetics.J. Pharmacokin. Biopharm. 6:547–558 (1978).CrossRefGoogle Scholar
  14. 14.
    O. Siddiqui, M. S. Roberts, and A. E. Polack. Topical absorption of methotrexate: Role of dermal transport.Int. J. Pharm. 27:193–203 (1985).CrossRefGoogle Scholar
  15. 15.
    P. Veng-Pedersen. Curve fitting and modeling in pharmacokinetics and some practical experiences with NONLIN and a new program FUNFIT.J. Pharmacokin. Biopharm. 5:513–531 (1977).CrossRefGoogle Scholar
  16. 16.
    H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimation in pharmacokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).CrossRefGoogle Scholar
  17. 17.
    R. J. Feldmann and H. I. Maibach. Regional variation in percutaneous penetration of14C cortisol in man.Arch. Dermatol. 48:181–183 (1967).Google Scholar
  18. 18.
    A. W. McKenzie. Percutaneous absorption of steroids.Arch. Dermatol. 86:611–614 (1962).CrossRefGoogle Scholar
  19. 19.
    A. J. Wickrema-Sinha, S. R. Shaw, and D. J. Weber. Percutaneous absorption and excretion of3H-diflorasone diacetate, a new topical corticosteroid in the rat, monkey and man.J. Invest. Dermatol. 71:372–377 (1978).PubMedCrossRefGoogle Scholar
  20. 20.
    P. M. Elias. Epidermal lipids, membranes and keratinisation.Int. J. Dermatol. 20:1–19 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    C. F. H. Vickers. Existence of reservoir in stratum corneum.Arch. Dermatol. 88:20–23 (1963).PubMedCrossRefGoogle Scholar
  22. 22.
    Y. W. Cheung, A. L. W. Po, and W. J. Irwin. Cutaneous biotransformation as a parameter in the modulation of the activity of topical corticosteroids.Int. J. Pharm. 26:175–189 (1985).CrossRefGoogle Scholar
  23. 23.
    J. Hadgraft. The epidermal reservoir: A theoretical approach.Int. J. Pharm 2:265–274 (1979).CrossRefGoogle Scholar
  24. 24.
    R. H. Guy and J. Hadgraft. Prediction of drug disposition kinetics in skin and plasma following topical adminstration.J. Pharm. Sci. 73:883–887 (1984).PubMedCrossRefGoogle Scholar
  25. 25.
    S. C. Valvani and S. H. Yalkowsky. Solubility and partitioning in drug design. In S. H. Yalkowsky, A. A. Sinkula, and S. C. Valvani (eds.),Physical Chemical Properties of Drugs, Marcel Dekker, New York 1980, pp. 220–221.Google Scholar

Copyright information

© Plenum Publishing Corporation 1989

Authors and Affiliations

  • O. Siddiqui
    • 1
  • M. S. Roberts
    • 1
  • A. E. Polack
    • 1
  1. 1.School of PharmacyUniversity of TasmaniaHobartAustralia

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