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Title: Evaluation of microdialysis as a tool for studying percutaneous drug absorption and cutaneous metabolism
Author: Keene, Warren Edward
ISNI:       0000 0001 3596 3366
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2002
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Cutaneous microdialysis is a method used to sample the extra-cellular fluid in dermal tissue. It uses a semi-permeable fibre, which is implanted in the dermis parallel to the skins surface. The fibre is perfused with a sterile physiological solution, which is collected at set periods. Low molecular weight compounds are able to diffuse freely into or out of the fibre in the direction of the concentration gradient. Once fibres have been implanted and are perfused, drug solutions can be applied to the skin surface directly above. Methyl salicylate (MeS) was the initial model drug. Occlusion of the drug site had no effect on the tissue Cmax but gave an increased AUC. Blood flow restriction using noradrenaline resulted in an increased Cmax and an increased AUC. Analysis for salicylic acid (the major metabolite) found higher concentrations than could be explained by the concentration present in the applied formulation, indicating that MeS was metabolised as it penetrated the skin. Comparisons of two vehicle formulations, one containing ethanol the other propylene glycol, showed that ethanol enhanced the transdermal absorption of methyl salicylate relative to the propylene glycol formulation. The transdermal absorption of salicylic acid and methyl salicylate was compared, salicylic acid gave the highest dermal concentrations despite being less lipophilic than methyl salicylate. MeS was introduced directly into the dermis via a microdialysis fibre in order to compare the metabolic activity of the epidermis to the dermis. Technical difficulties were encountered but the data indicated that MeS is metabolised in the dermis though to a lesser degree than in the epidermis. Ketoprofen was used to study the dialysis of highly protein bound drug, it has a literature protein binding value of 95%. Two fibres were used, a 2kDa fibre, which only dialysed free drug, and a 3MDa fibre, which dialysed both free and protein bound drug. The 3MDa fibres dialysed a higher concentration of ketoprofen however the increase was due to the increased efficiency of 3MDa fibres to dialyse free drug.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Skin