Diclofenac epolamine (Flector) patch: evidence for topical activity.
This review focuses on previously unpublished clinical and pharmacokinetic data with the diclofenac epolamine (diclofenac hydroxyethylpyrrolidine) patch supporting the hypothesis of a topical effect of this formulation. Previous studies have shown that 1 or 2 weeks of treatment with diclofenac epolamine provides pain relief for various localized musculoskeletal conditions such as ankle sprains, epicondylitis and knee osteoarthritis. The reduction in pain after application of the first patch in 155 patients with painful knee osteoarthritis was significant at the 1-hour time point and was superior to placebo at the 3-hour time point and at all time points thereafter. Comparable results were found in a study of 274 patients with acute ankle sprains, in which pain relief was also significantly superior to placebo at the 3-hour time point. Corresponding single-dose (patch) application for 12 hours in ten healthy volunteers demonstrated that diclofenac first appears in plasma at a mean of 4.5 hours after application (range 2-8 hours). Hence, the patch provided pain relief at a time point at which no diclofenac is assumed to be in plasma, which demonstrates local action in terms of tissue diclofenac accumulation under the patch. This is further supported by an apparent plasma diclofenac half-life of 9-12 hours after patch application, which implies the presence of a tissue reservoir, as the half-life after oral intake of diclofenac is 1-2 hours.Steady-state plasma diclofenac concentrations are present before 3 days' application (two patches/day) and are in the order of 1-3 ng/mL. The bioavailability in terms of systemic exposure from the patch compared with oral intake (75 mg/day) is in the order of 1%. Such low diclofenac concentrations are without systemic effects, as demonstrated by the fact that no drug-related gastrointestinal bleeding, ulcers or cutaneous events characteristic of Steven-Johnson syndrome have been reported during 15 years of diclofenac epolamine patch use.These data provide support for the notion that diclofenac epolamine patch provides pain relief through accumulation of diclofenac under the site of application, without any evidence of systemic effects.
Petersen
Birte
B
Research & Development Department, IBSA Institut Biochimique SA, Pambio-Noranco, Lugano, Switzerland. birtepetersen@dadlnet.dk
Rovati
Stefano
S
D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D009140:Musculoskeletal Diseases / Q000188:drug therapy* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac