Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies.
OBJECTIVE
The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site.


METHODS
The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes.


RESULTS
The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels ofsalicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations.


CONCLUSIONS
The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply.
Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
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Cross
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Anderson
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Roberts
D000287:Administration, Topical; D000328:Adult; D002478:Cells, Cultured; D004058:Diffusion; D005260:Female; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D012459:Salicylates / Q000493:pharmacokinetics*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D012869:Skin Absorption
D012459:Salicylates; C020904:glycol salicylate; C032758:trolamine salicylate; C033069:methyl salicylate