Objective assessment of topical corticosteroids and non-steroidal anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation.
The aim of this study was to compare the activities of the two main classes of topical anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation, using a new methodology based on laser-Doppler velocimetry. Six topical non-steroidal anti-inflammatory drugs (NSAIDs) (bufexamac, diclofenac, ibuprofen, indomethacin, phenylbutazone and niflumic acid) and three topical corticosteroids (clobetasol propionate, hydrocortisone and hydrocortisone butyrate) were tested. Drugs were commercially available (except indomethacin) and were applied under occlusion for 4 h to the forearms of 16 healthy male volunteers. Thirty minutes after excess drug removal, skin inflammation was induced by a 1-min application of methyl nicotinate (3 mM). This was repeated 44 h later. Each methyl-nicotinate application was followed by continuous skin blood flow recordings over 1 h. Overall, NSAIDs proved more effective than corticosteroids in inhibiting methyl-nicotinate-induced increases in skin blood flow. Diclofenac and indomethacin showed a potent prolonged inhibitory effect. Different types of activity were observed in the corticosteroid group: (a) At 30 min, hydrocortisone and hydrocortisone butyrate moderately inhibited methyl-nicotinate reactions whereas clobetasol propionate produced no detectable effects; (b) at 44 h, clobetasol propionate produced a significant inhibition whereas hydrocortisone butyrate and hydrocortisone exhibited either weak or no inhibitory action at all. These pharmacodynamic discrepancies between the corticosteroids tested could be related to differences in drug affinity to cutaneous receptors and in vasoconstrictive potency.
Duteil
L
L
Centre de Pharmacologie Clinique Appliquee a la Dermatologie (CPCAD), Nice, France.
Queille
C
C
Poncet
M
M
Ortonne
J P
JP
Czernielewski
J
J
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001623:Betamethasone / Q000031:analogs & derivatives*; D002019:Bufexamac / Q000627:therapeutic use; D002990:Clobetasol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003877:Dermatitis, Contact / Q000517:prevention & control*; D004008:Diclofenac / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use*; D007052:Ibuprofen / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D009539:Nicotinic Acids / Q000009:adverse effects*; D009544:Niflumic Acid / Q000627:therapeutic use; D010653:Phenylbutazone / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009539:Nicotinic Acids; C007975:hydrocortisone-17-butyrate; D004008:Diclofenac; D002019:Bufexamac; D009544:Niflumic Acid; C008473:methyl nicotinate; D001623:Betamethasone; D002990:Clobetasol; D010653:Phenylbutazone; D006854:Hydrocortisone; D007052:Ibuprofen; D007213:Indomethacin