科研之友
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摘要
AIMS
To evaluate the relative plasma and tissue availability of diclofenac after repeated topical administration of a novel diclofenac acid-based delivery system under development (DCF100C).
METHODS
This was a single-centre, open-label, three-period, crossover clinical trial of five discrete diclofenac formulations. Test preparations comprised two concentrations (1.0% and 2.5%) of DCF100C, with and without menthol and eucalyptus oil (total daily doses of 5 mg and 12.5 mg). Voltaren (R) Emulgel (R) gel (1.0%) was the commercially available comparator (total daily dose of 40 mg). Topical application was performed onto the thigh of 20 male healthy subjects for 3 days. Applying a Youden square design, each drug was evaluated in 12 subjects, with each subject receiving three test preparations. Blood sampling and in vivo microdialysis in subcutaneous adipose and skeletal muscle tissues were performed for 10 h after additional final doses on the morning of day 4.
RESULTS
All four DCF100C formulations demonstrated a three- to fivefold, dose-dependent increase in systemic diclofenac availability compared with Voltaren (R) Emulgel (R) and were approximately 30-40 times more effective at facilitating diclofenac penetration through the skin, taking different dose levels into account. Tissue concentrations were low and highly variable. The 2.5% DCF100C formulation without sensory excipients reached the highest tissue concentrations. AUC(0,10 h) was 2.71 times greater than for Voltaren (R) Emulgel (R) (90% CI 99.27, 737.46%). Mild erythema at the application site was the most frequent adverse event associated with DCF100C. There were no local symptoms after treatment with the reference formulation.
CONCLUSION
DCF100C formulations were safe and facilitated greater diclofenac penetration through the skin compared with the commercial comparator. DCF100C represents a promising alternative to oral and topical diclofenac treatments that warrants further development.
- 出版日期2011-6
