Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine

• Published in: Current medical research and opinion 2008-10, Vol.24 (10), p.2967-2992
• Main Authors: Rainsford, K. D., Kean, W. F., Ehrlich, G. E.
• Format: Article
• Language: English
• Subjects: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Bone Diseases - drug therapy; Bone Diseases - metabolism; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; Diclofenac; Diclofenac - adverse effects; Diclofenac - analogs & derivatives; Diclofenac - pharmacokinetics; Diclofenac - pharmacology; Humans; Inflammation - drug therapy; Inflammation - metabolism; Muscular Diseases - drug therapy; Muscular Diseases - metabolism; Musculoskeletal pain; Pain - drug therapy; Pain - metabolism; Percutaneous; Pharmacokinetics; Skin - metabolism; Sports injuries; Topical NSAIDs
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/03007990802381364

ABSTRACT Background: Topical formulations of non-steroidal anti-inflammatory drugs (NSAIDs), in particular diclofenac (DI), have become popular for treating various acute and chronic painful inflammatory conditions. Objective: To perform a literature review of (1) the use of topical NSAIDs; (2) the pharmaceutical, pharmacokinetic and pharmacodynamic properties of a medicated plaster (patch) containing diclofenac epolamine (DI-EP, Flector Tissugel, Flector patch*) compared with other formulations of topical NSAIDs; and (3) evaluation of the clinical findings from studies with this novel DI-EP patch. Outcomes: (1) Pharmacokinetic studies involved determination of DI from DI-EP and separately epolamine (EP) and the epoxide metabolite (N-oxide-EP) in laboratory animals and humans; the latter being the major metabolite in humans. About 2% of DI is absorbed by the skin in humans and is excreted in the urine. Maximum plasma concentrations of 17.4 ng/mL DI are reached at 5.4 hours (approximate steady state conditions); the plasma elimination half-time (t½) being 26.4 hours. Low systemic levels of DI and EP are produced from DI-EP. Pronounced accumulation of DI occurs in the muscle layers and in synovial fluids of arthritic patients; (2) No significant toxicity occurs from EP nor N-oxide-EP, while that of oral DI-EP was similar to that from DI; and (3) In acute musculoskeletal conditions (sprains, tendonitis and sports injuries) and osteoarthritis DI-EP patches control pain and signs of joint or physical injury compared with placebo controls by 3-5 days with almost complete pain relief at 14 days. DI-EP was shown to have equivalent therapeutic effect to another DI diethylammonium gel formulation (Voltaren Emulgel†). There were no reports of serious adverse events in the gastro-intestinal (GI) tract, kidneys or liver from DI-EP. Mild GI symptoms and skin reactions occur in 2 and10% of patients, respectively. Conclusions: The patch delivery of DI in DI-EP affords controlled delivery of the active drug in contrast to that from application of gels or ointments of NSAIDs.