The effect of aging on percutaneous absorption in man.
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 (greater than 65 years) subjects. Standard radiotracer methodology was employed and PA was quantified from the urinary excretion profiles of 14C 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 less than 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.
Roskos
K V
KV
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Maibach
H I
HI
Guy
R H
RH
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000652:urine; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D001565:Benzoates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D019817:Benzoic Acid; D002110:Caffeine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D004958:Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D006801:Humans; D006854:Hydrocortisone; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012869:Skin Absorption; D013739:Testosterone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine
D000893:Anti-Inflammatory Agents; D001565:Benzoates; D002110:Caffeine; D013739:Testosterone; D004958:Estradiol; D019817:Benzoic Acid; D001241:Aspirin; D006854:Hydrocortisone