PERCUTANEOUS-ABSORPTION OF DICLOFENAC

  • 1 January 1986
    • journal article
    • research article
    • Vol. 36-2  (7) , 1092-1096
Abstract
The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenace in human urine was the same after topical and oral administration. In man, upon daily topical administration of 13 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l. Topical adminstration of 4 times daily 2.5 g of the Emulgel formulation on the hands of 8 arthritic patients for 3 days, with a last dose 1-3 h before hand surgery on day 4, produced diclofenac concentrations of .gtoreq. nmol/l in plasma, of .gtoreq. 370 nmol/l in synovial fluid and of .gtoreq. 410 nmol/kg in synovial tissue.

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