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Central and peripheral tissue distribution of diclofenac after subcutaneous injection in the rat

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image of Inflammopharmacology

Nonsteroidal anti-inflammatory drugs (NSAIDs) are viewed as peripherally acting analgesics; however, evidence is accruing that they also act centrally. To help clarify the regional actions of diclofenac, we studied its plasma and tissue concentrations after subcutaneous injection in a model of acute pain, the rat tail ischaemia-reperfusion acute hyperalgesia model. After antinociceptive doses (20 and 40 mg kg-1), diclofenac plasma Cmax occurred at ~ 20 min and neither plasma or tissue concentrations were affected by application of the pain model. Brain, spinal cord, heart, skeletal muscle, (injured) tail cartilaginous tissue, stomach and fat had similar distribution coefficients (0.05-0.2). Distribution coefficients for liver (0.5-1.4) and kidney (0.3-0.5) increased with time, presumably reflecting their roles in the elimination of diclofenac. Subcutaneous injection was found a pharmacokinetically reliable method for administering diclofenac for antinociception studies in the rat. The finding that CNS and peripheral tissue distribution coefficients of diclofenac were similar provides indirect support for a potential central action of NSAIDs.


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