Effect of sodium lauryl sulfate-induced skin irritation on in vitro percutaneous absorption of four drugs.
The influence of irritant contact dermatitis on 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 in vivo 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 animals were sacrificed. Percutaneous penetration was then measured using in vitro diffusion cells and the removed (pretreated) skin. The following parameters were determined: cumulative amount of compound penetrated, steady state flux, lag time, and permeability coefficient, skin concentration per unit area, and the relative amount of drug remaining in the skin (as a percentage of the cumulative amount of compound penetrated through the skin). SLS pretreatment resulted in moderate irritant dermatitis in all animals and increased in vivo transepidermal water loss 4.5 times. Flux was increased in SLS-pretreated skin as compared with controls for all four compounds, with the greatest enhancement for hydrocortisone (HC) (5.9 times), followed by indomethacin (IM) (4.6 times), ibuprofen (IB) (3.9 times), and acitretin (AC) (3.4 times). Skin concentrations increased to a smaller degree from 1.6 times (IB) and 2.6 times (HC) to 3.4 times (IM). However, AC skin concentrations were not different between the two groups. Thus, percutaneous penetration parameters were equivocally influenced by SLS-induced irritation. Increased skin concentrations were paralleled by even higher increases in flux.
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; D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics; D001834:Body Water / Q000378:metabolism; D003877:Dermatitis, Contact / Q000209:etiology / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006854:Hydrocortisone; D007052:Ibuprofen / Q000493:pharmacokinetics; D007213:Indomethacin / Q000493:pharmacokinetics; D012869:Skin Absorption / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin / Q000031:analogs & derivatives / Q000493:pharmacokinetics
D000893:Anti-Inflammatory Agents; D012967:Sodium Dodecyl Sulfate; D014212:Tretinoin; D017255:Acitretin; D006854:Hydrocortisone; D007052:Ibuprofen; D007213:Indomethacin