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


RESULTS
(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 (t(1/2)) 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 and 10% 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.
Rainsford
K D
KD
Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK. k.d.rainsford@shu.ac.uk
Kean
W F
WF
Ehrlich
G E
GE
D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001847:Bone Diseases / Q000188:drug therapy / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000494:pharmacology; D004008:Diclofenac / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D009135:Muscular Diseases / Q000188:drug therapy / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac