Abstract
Despite much research into the mechanisms of cutaneous aging and the identification of significant age-associated biological and biophysical changes within the skin, the question “How does aging affect percutaneous absorption (PA) in vivo?” remains unanswered. We have made in vivo measurements of PA in young (18–40 years) and old (>65 years) subjects. Standard radiotracer methodology was employed and PA was quantified from the urinary excretion profiles of14C radiolabel (corrected for incomplete renal elimination). Testosterone (TST), estradiol (EST), hydrocortisone (HC), benzoic acid (BA), acetylsalicylic acid (ASA), and caffeine (CAFF) have been studied. Permeation of HC, BA, ASA, and CAFF was significantly (p <0.01, 0.01, 0.01, and 0.05, respectively) lower in aged subjects, whereas the absorption of TST and EST was similar in the two groups. Thus it appears that aging can affect PA in vivo and that relatively hydrophilic compounds are particularly sensitive. The diminished surface lipid content of “old” skin implies a diminished dissolution medium for compounds administered topically. It is reasonable to speculate that this physiologic change will impact most severely upon those permeants whose lipid solubility is lowest (that is, HC, BA, ASA, CAFF). Furthermore, the typically reduced hydration of aged stratum corneum will compound this effect for these chemicals. Conversely, highly lipid-soluble chemicals (TST and EST) may still be able to dissolve readily into the stratum corneum even when the available lipid medium is reduced.
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References
B. A. Gilchrest.Skin and Aging Processes. CRC Press, Boca Raton, FL, 1984.
R. O. Potts, E. M. Buras, and D. A. Chrisman. Changes with age in the moisture content of human skin.J. Invest. Dermatol. 82:97–100 (1984).
R. O. Potts and E. M. Buras. In vivo changes in the dynamic viscosity of human stratum corneum as a function of age and ambient moisture.J. Soc. Cosmet. Chem. 36:169–176 (1985).
P. E. Pochi, J. S. Strauss, and D. T. Downing. Age-related changes in sebaceous gland activity.J. Invest. Dermatol. 73:108–111 (1979).
R. M. Lavker, P. Zheng, and G. Dong. Morphology of aged skin. In B. A. Gilchrest (ed.),Dermatologic Clinics: The Aging Skin, W. B. Saunders, Philadelphia, 1986, pp. 379–389.
T. J. Ryan. Cutaneous circulation. In L. A. Goldsmith (ed.),Biochemistry and Physiology of the Skin, Oxford University Press, New York, 1983, pp. 817–877.
L. B. Fisher. In vitro studies on the permeability of infant skin. In R. L. Bronaugh and H. I. Maibach (eds.),Percutaneous Absorption, Marcel Dekker, New York, 1985, pp. 213–222.
J. J. McCormack, E. K. Boisits, and L. B. Fisher. An in vitro comparison of the permeability of adult versus neonatal skin. In H. I. Maibach and E. K. Boisits (eds.),Neontal Skin: Structure and Function, Marcel Dekker, New York, 1982, pp. 149–166.
D. R. Wilson and H. I. Maibach. An in vivo comparison of skin barrier function. In: H. I. Maibach and E. K. Boisits (eds.),Neonatal Skin: Structure and Function. Marcel Dekker, New York, 1982, pp. 101–110.
R. J. Feldmann and H. I. Maibach. Percutaneous penetration of steroids in man.J. Invest. Dermatol. 52:89–94 (1969).
R. J. Feldmann and H. I. Maibach. Absorption of some organic compounds through the skin in man.J. Invest. Dermatol. 54:399–404 (1970).
E. Christophers and A. M. Kligman. Percutaneous absorption in aged skin. In W. Montagna (ed.),Advances in Biology of the Skin, Vol. 6, Aging, Pergamon Press, Oxford, 1965, pp. 163–175.
H. Tagami. Functional characteristics of aged skin. 1. Percutaneous absorption.Acta Derm. (Kyoto) 67:19–21 (1972).
R. S. Hinz, C. D. Hodson, C. R. Lorence, and R. H. Guy. In vitro percutaneous penetration: Evaluation of the utility of hairless mouse skin.J. Invest. Dermatol. 93:87–91 (1989).
D. A. W. Bucks, H. I. Maibach, and R. H. Guy. Mass balance and dose accountability in percutaneous absorption studies: Development of a nonocclusive application system.Pharm. Res. 5:313–315 (1988).
D. A. W. Bucks, J. P. L. Marty, and H. I. Maibach. Percutaneous absorption of malathion in the guinea pig: Effect of repeated skin application.Food Chem. Toxicol 23:919–922 (1985).
D. A. W. Bucks, J. R. McMaster, H. I. Maibach, and R. H. Guy. Bioavailability of topically administered steroids: A “mass balance” technique.J. Invest. Dermatol. 90:29–33 (1988).
A. Leo, C. Hansch, and D. Elkins. Partition coefficients and their uses.Chem. Rev. 71:525–616 (1971).
S. Riegelman and P. Collier. The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time.J. Pharm. Biopharm. 8:509–534 (1980).
E. Nakashima and L. Z. Benet. General treatment of mean residence time, clearance and volume parameters in linear mamillary models with elimination from any compartment.J. Pharm. Biopharm. 16:475–492 (1988).
S. E. Friberg and D. W. Osborne. Small angle x-ray diffraction patterns of stratum corneum and a model structure for its lipids.J. Disper. Sci. Tech. 6:485–495 (1985).
S. E. Friberg and D. W. Osborne. Interaction of a model skin surface lipid with a glyceridacid.J. Am. Oil Chem. Soc. 63:123–126 (1986).
A. Rougier, C. Lotte, and H. I. Maibach. In vivo relationship between transepidermal water loss and percutaneous absorption in man.Clin. Res. 36:690A (1988).
G. L. Grove, S. Duncan, and A. M. Kligman. Effect of aging on the blistering response of human skin with ammonium hydroxide.Br. J. Dermatol. 107:393–400 (1982).
R. Scheuplein and L. Ross. Effects of surfactants and solvents on the permeability of epidermis.J. Soc. Cosmet. Chem. 21:853–873 (1970).
I. H. Blank. The effect of hydration on the permeability of the skin. In R. L. Bronaugh and H. I. Maibach (eds.),Percutaneous Absorption, Marcel Dekker, New York, 1985, pp. 97–105.
M. Nazzaro-Porro, S. Passi, L. Boniforti, and F. Belsito. Effects of aging on fatty acids in skin surface lipids.J. Invest. Dermatol. 73:112–117 (1979).
A. Yamamoto, S. Serizawa, M. Ito, and Y. Sato. Effect of aging on sebaceous gland activity and on the fatty acid composition of wax esters.J. Invest. Dermatol. 89:507–512 (1987).
S. J. DeSalva and G. Thompson. Na22Cl skin clearance in humans and its relation to skin age.J Invest. Dermatol. 45:315–318 (1965).
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This work was supported by a grant (GM-33395) from the U.S. National Institutes of Health to RHG.
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Roskos, K.V., Maibach, H.I. & Guy, R.H. The effect of aging on percutaneous absorption in man. Journal of Pharmacokinetics and Biopharmaceutics 17, 617–630 (1989). https://doi.org/10.1007/BF01062121
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DOI: https://doi.org/10.1007/BF01062121