Diclofenac systemic bioavailability of a topical 1 diclofenac+3 menthol combination gel vs. an oral diclofenac tablet in healthy volunteers: a randomized, open-label, crossover study

摘要

Objective: Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1 diclofenac sodium and 3 menthol in either of 2 formulation packages relative to oral administration. Methods: In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1 diclofenac + 3 menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1 diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods. Results: A total of 18 subjects enrolled and completed the study. Relative to oral administration, area under the concentration time curve from 48 to 72 hours (AUC(48-72)) with topical administration of 1-diclofenac + 3 menthol gel from a tube or roll-on device was 16.1 (90 CI: 12.2 - 21.1) and 14.4 (90 CI: 11.0 - 19.0), respectively. The diclofenac/menthol combination delivered significantly higher exposures of diclofenac compared with Voltaren Gel. A higher number of adverse events (AEs) occurred with the topical diclofenac/menthol combination (61) vs. Voltaren Gel (22) or oral diclofenac (6); most were local skin reactions. No difference in systemic AEs was observed among the groups. Conclusion: As expected, systemic exposure was significantly lower with the topical diclofenac/menthol treatment regimens compared with oral diclofenac. Local skin AEs were increased with the topical combination product, but the risk of systemic AEs was low.