Effect of lecithin on epicutaneous absorption of diclofenac epolamine.
The epicutaneous application of nonsteroidal antiinflammatory drugs in localized rheumatic diseases results in a highly targeted antiinflammatory action and is associated with reduced systemic effects. The new diclofenac epolamine (DHEP) salt is much more soluble both in water and in lipid solvent than other diclofenac salts. The pharmaceutical addition of lecithin to DHEP leads to the formation of mixed micelles with high affinity to the cellular component, which guarantees the absorption of the active ingredient. We performed a bioavailability randomized, cross-over study to compare the plasma profiles of diclofenamic acid after repeated epicutaneous administration of the new topical formulation with those of the marketed DHEP formulation without lecithin. Based on a randomization list, 12 healthy volunteers were asked to apply one of the two formulations twice a day for 10 consecutive days. The other formulation was given after a washout period of 1 week. Blood samples were collected before the morning epicutaneous dose on days 1, 3, 5 and 8 of treatment and on day 10 at different sampling times until 24 h after the application. The pharmacokinetic analysis showed a significantly higher plasma concentration of diclofenamic acid after the application of DHEP lecithin, which indicates a better saturation of the subcutaneous tissues underlying the application site. This also indicates increased local availability of the active principle. In conclusion, the new DHEP formulation with lecithin should have a therapeutic advantage compared with the formulation without lecithin, even in cases of short- to medium-term treatments.
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Department of Agricultural Sciences, University of Modena and Reggio Emilia, Reggio Emilia, Italy.
Ronca
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Petrini
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Mautone
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D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005542:Forearm; D005782:Gels; D006801:Humans; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000737:chemistry*; D012869:Skin Absorption / Q000187:drug effects*
D000277:Adjuvants, Pharmaceutic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D010713:Phosphatidylcholines; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac