The amount of diclofenac absorbed through the skin is proportional to the area of the treated surface and depends on both the total dose of the drug applied and the degree of hydration of the skin.
After application to the skin surface area of 400 cm2 Voltaren® Emulgel®, gel for external use 2% (2 applications per day), the concentration of the active substance in the plasma corresponds to its concentration when using 1% diclofenac gel (4 applications per day). On the 7th day, the relative bioavailability of the drug (AUC ratio) is 4.5% (for the equivalent dose of the sodium salt of diclofenac). When wearing a moisture-permeable bandage, the absorption did not change.
The concentration of diclofenac in plasma, synovial membrane and synovial fluid was measured when the drug was applied to the area of the affected joint. The maximum concentrations in the plasma were approximately 100 times lower than after oral administration of the same amount of diclofenac. 99.7% of diclofenac is bound by plasma proteins, mainly with albumins (99.4%).
Diclofenac is predominantly distributed and retained deep in tissues prone to inflammation, such as joints, where its concentration is 20 times higher than in plasma.
The metabolism of diclofenac is partly due to glucuronization of the unmodified molecule, but mainly through single and multiple hydroxylation, which leads to the formation of several phenolic metabolites, most of which are converted into glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
The total systemic plasma clearance of diclofenac is 263 ± 56 ml / min. The final half-life is 1-2 hours. The half-life of metabolites, including two pharmacologically active metabolites, is also short-lived and is 1-3 hours.One of the metabolites (3'-hydroxy-4'-methoxydiclofenac) has a longer half-life, but this metabolite is completely inactive. Most of the diclofenac and its metabolites are excreted in the urine.