Effects of local blood flow on the percutaneous absorption of the organophosphorus compound malathion: a microdialysis study in man.
Malathion [O,O-dimethyl-S-(1,2-dicarbethoxyethyl)phosphorodithioate] is an organophosphorus insecticide widely used in veterinary medicine and in humans for the treatment of lice. In this study, the rate of the percutaneous absorption of malathion has been measured in human skin, in vivo, using microdialysis. Malathion was detected in tissue dialysate within 30 min of its topical application to the skin of the volar surface of the forearm of healthy volunteers. The concentration of malathion in dialysate increased with lengthening duration of exposure to reach a steady state concentration at 2 h. Prolonged exposure to malathion caused a marked and long-lasting erythema localized to the area of contact. There was no evidence of local tissue oedema or of a neurogenically mediated flare or itch response following topical application. Reducing skin blood flow by the addition of the vasoconstrictor noradrenaline to the dialysis probe perfusate caused an eight-fold increase in the recovery of malathion in the dialysate, which failed to reach a steady state within 5 h. Together, these data confirm that malathion can be absorbed percutaneously and that its distribution within the cutaneous tissue space is influenced by local skin blood flow. They suggest that the increase in skin blood flow caused by malathion may itself play a significant role in enhancing its systemic uptake.
Boutsiouki
P
P
Dermatopharmacology Unit, Allergy and Inflammation Sciences, School of Medicine, University of Southampton, UK.
Thompson
J P
JP
Clough
G F
GF
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D005260:Female; D005782:Gels; D006801:Humans; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017078:Laser-Doppler Flowmetry; D008294:Malathion / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000378:metabolism*; D012869:Skin Absorption; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D005782:Gels; D007306:Insecticides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D008294:Malathion; D009638:Norepinephrine