Penetration of topical diclofenac sodium 4 % spray gel into the synovial tissue and synovial fluid of the knee: a randomised clinical trial

Abstract

Diclofenac sodium 4 % spray gel was found to penetrate the skin locally in substantial amounts and thus reach the desired target tissue. Concentrations were not dose-dependent, and application was well tolerated by 97.4 % of patients. Topical application of diclofenac should be considered a valuable alternative to systemic NSAID therapy in the initial treatment of osteoarthritis.

Pharmacokinetics of Transdermal Etofenamate and Diclofenac in Healthy Volunteers

“…After repetitive administration, the plasma trough concentrations were higher by a factor of approximately 2.5 for diclofenac (reaching 1.5 ng/mL or approximately 5 nmol/L) and 1.8 for flufenamic acid (reaching 50 ng/mL or approximately 180 nmol/L) compared to the C max after a single dose. These plasma concentrations were in the same range as reported in other studies for both diclofenac [21,25] and flufenamic acid [18]. In comparison with the reported IC 50 values for COX-1 (75 nmol/L for diclofenac and 3 lmol/L for flufenamic acid) and COX-2 (38 nmol/L for diclofenac and 9.3 lmol/L for flufenamic acid) [27], the plasma concentrations reached were clearly lower, again explaining the lack of dose-dependent adverse drug reactions.…”

“…The values obtained after administration of a single patch (0.22% for diclofenac and of 1.15% for etofenamate) were substantially lower than those reported for cutaneous absorption, which were 6% for diclofenac and 21% for etofenamate . This discrepancy can be explained by accumulation in the skin and in adjacent tissues such as fat, skeletal muscle and ligaments, where mostly much higher concentrations are reached than in blood . Moreover, the relative bioavailability is also influenced by the drug formulation itself.…”

Skin penetration and tissue permeation after topical administration of diclofenac

“…It seems that topical NSAIDs are currently underutilized 14 , and their efficacy in pain relief remains debatable 15 . Clinicians still seem to be unsure of the value of topical NSAIDs 16 , with many regarding them as little more than placebo 15 . Indeed, a large placebo effect of around 50% (after 12 weeks) has been observed in studies of topical NSAIDs, twice as high as that in studies with oral placebo (25% in a pooled analysis) 15 .…”

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

“…It is well established that topical diclofenac penetrates the skin, permeates underlying tissues, and enters the synovium (Fig. 2) [63][64][65][66]. Analgesic efficacy may be dependent on diclofenac concentration in the synovial compartment, the site of diclofenac's activity.…”

“…Analgesic efficacy may be dependent on diclofenac concentration in the synovial compartment, the site of diclofenac's activity. However, reports of the relative distribution of diclofenac following topical administration in joint tissue (the ''effect compartment'') and in plasma (a ''side effect compartment'') are variable [65][66][67][68], and the minimum concentration needed in plasma or synovial tissue to achieve a meaningful reduction in pain intensity is still poorly defined.…”