Effect of sodium lauryl sulfate-induced skin irritation on in vivo percutaneous penetration of four drugs.
The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.
Wilhelm
K P
KP
Department of Dermatology, School of Medicine, University of California San Francisco 94143-0989.
Surber
C
C
Maibach
H I
HI
D017255:Acitretin; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003877:Dermatitis, Contact / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D012867:Skin / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects; D012967:Sodium Dodecyl Sulfate / Q000009:adverse effects*; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin; D017255:Acitretin; D006854:Hydrocortisone; D007052:Ibuprofen; D007213:Indomethacin