Probing the skin permeation of eicosapentaenoic acid and ketoprofen 2. Comparative depth profiling and metabolism of eicosapentaenoic acid.
Unexpected enhancement of the topical delivery of eicosapentaenoic acid (EPA) across porcine skin was observed previously when fish oil was co-formulated with ketoprofen. In the current work depth profile analysis was used to probe the epidermal conversion of EPA to its 15-hydroxy metabolite in the presence and absence of ketoprofen. Freshly excised full-thickness porcine skin in Franz diffusion cells was dosed (both infinite and finite) with simple formulations based on fish oil as source of EPA. After 24h the skin was subjected to tape stripping and depth profiles were constructed. Typical depth profiles were obtained, with an inverse relationship between depth and permeant concentration. 15-HEPE was generated in the skin when Hepes-modified Hanks' balanced salt solution was used, but none was detected when a cetrimide receptor phase was used, highlighting the importance of maintaining skin viability in such exercises. Ketoprofen had a direct influence on the metabolism of EPA and resulting in conversion to its 15-LOX metabolite 15-HEPE. However, this link appears to be only part of the solution of EPA enhancement however, as even in non-viable skin ketoprofen had an enhancing affect.
Thomas
Christopher P
CP
Welsh School of Pharmacy, Cardiff University, Wales, UK.
Heard
Charles M
CM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D003627:Data Interpretation, Statistical; D015194:Diffusion Chambers, Culture; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D005395:Fish Oils; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000493:pharmacokinetics*; D010539:Permeability / Q000187:drug effects; D011955:Receptors, Drug / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D005395:Fish Oils; D011955:Receptors, Drug; D007660:Ketoprofen; C059164:15-hydroxy-5,8,11,13,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid