RESUMO
BACKGROUND: The favorable benefit-risk profile of topical nonsteroidal anti-inflammatory drugs (NSAIDs) makes them a preferred treatment for pain relief in soft tissue injuries. PURPOSE: To assess the efficacy and safety of a novel etofenamate 70-mg medicated plaster in patients with acute uncomplicated ankle sprain. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients with grade 1 or 2 ankle sprain of recent onset were randomized to etofenamate or placebo plasters (1:1) applied twice daily for 7 days. Clinical assessments, including ankle pain on movement (POM) in mm on a 100-mm visual analog scale (VAS), were made at predefined intervals during the treatment period. RESULTS: In total, 156 male or female adult patients (mean age, 35.3 ± 11.8 years) were enrolled. The fall in VAS values for POM from baseline to 72 hours was markedly in favor of the etofenamate plaster, with respective reductions of 52.7% and 24.0% for active and placebo plasters (least squares mean treatment difference, 22.1 mm; P value for analysis of covariance < .0001). Similar clinically relevant differences between etofenamate and placebo were seen for POM at the 48-, 96-, and 168-hour visits (P < .0001). These differences between etofenamate and placebo plasters were reflected in area under the curve for POM, pain at rest, and ankle swelling measured at various time points during the 7 days. Time taken to achieve a meaningful (30%) and optimal (50%) reduction of POM was significantly shorter in the etofenamate group. The responder rate (proportion of patients with at least 50% pain reduction at 72 hours) was 52.5% for the etofenamate plaster and 7.7% for the placebo. A significantly greater proportion of patients randomized to etofenamate rated their progress and/or the treatment as "good" or "very good." The medicated plasters adhered well over the 12-hour dosing period and were very well-tolerated. CONCLUSION: With respect to the investigated indication, uncomplicated ankle sprain, the etofenamate plaster has therapeutic efficacy that is similar to that for the best available topical NSAID formulations. REGISTRATION: 2016-000252-99 (EudraCT number).
RESUMO
Little is known about the course of the plasma concentration and the bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) contained in dermal patches. We compared an etofenamate prototype patch (patent EP 1833471) and a commercially available diclofenac epolamine patch regarding the bioavailability of the active ingredients relative to respective i.m. applications and regarding their plasma concentration-time course. Twenty-four healthy human volunteers were treated using a parallel group design (n = 12 per group) with a single dermal patch (removed after 12 hr) followed (after a latency of 48 hr) by eight consecutive dermal patches every 12 hr to reach steady-state conditions. The patches were generally well tolerated, but one volunteer treated with etofenamate developed an allergic contact dermatitis. After the first patch, Cmax was 0.81 ± 0.11 (mean ± S.E.M.) ng/mL (reached 12 hr after patch removal) for diclofenac and 31.3 ± 3.8 ng/mL for flufenamic acid (reached at patch removal), the main metabolite of etofenamate. Etofenamate was not detectable. After repetitive dosing, trough plasma concentrations after the eighth dose were 1.72 ± 0.32 ng/mL for diclofenac and 48.7 ± 6.6 ng/mL for flufenamic acid. Bioavailabilities (single dose) relative to i.m. applications were 0.22 ± 0.04% for diclofenac and 1.15 ± 0.06% for flufenamic acid. In conclusion, the relative bioavailability (compared to the respective i.m. application) of both drugs is low. The maximal plasma concentrations after topical administration of these drugs are well below the IC50 values for COX-1 and COX-2, explaining the absence of dose-dependent toxicities.
