Diclofenac sodium is a nonsteroidal antiinflammatory drug (NSAID) that has been used in 120 countries since its introduction in Japan in 1974. It is currently the eighth largest-selling drug and the most frequently used NSAID in the world. Diclofenac, a phenylacetic acid derivative, is a potent inhibitor of cyclooxygenase enzyme activity, and may also interact with the lipoxygenase enzyme pathway, and with the release and reuptake of arachidonic acid. Diclofenac is almost completely absorbed, highly protein-bound, penetrates well into synovial fluid, and is extensively metabolized. Comparative studies have shown that diclofenac is at least equivalent in efficacy to aspirin and other NSAID when used for the treatment of rheumatic diseases such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Diclofenac also possesses potent analgesic properties. Clinical trials suggest that diclofenac has a favorable side-effect profile, excellent patient tolerability, and a lower patient dropout rate when compared with aspirin and other NSAID.
Seven days after intravenous administration to rats of 3.32 x 104-5.36 x lo3 mmol of isotopic-or carricr-diluted PmCl,, the fraction of injected, monomeric promethiurn retained in the skelton was greatest at the lowest mass administered. Generally no m a s effect was observed in kidney, liver or spleen at the monomeric m a s levels administered.The effectiveness of 0.3 mmole diethylenetriaminepentaacetic acid (DTPA) in decreasing the fraction of injected promethium retained in the skeleton following prompt (1 hr) or delayed (48 hr) treatment was less for the lowest mass injected than for other monomeric masses. In the soft tissues, a relatively constant fraction of the control rats' promethium tissue burden was removed by DTPA treatment at all monomeric mass levels. At the highest mass level, particulate formation typically altered the distribution as well as effectiveness of DTPA treatments. While the amount of promethium removed from most of the examined tissues by DTPA treatments at each monomeric level, was an almost constant fraction of that retained in the control tissues, the moles of promethium being removed increased with injected mass as the molar ratio of DTPA:Pm varied from loQ to lo5.In extending the results of animal experiments and tracer-level human experimcnts as predictors of radionuclide retention and of the efficacy of removal procedures in accidental human exposurc situations, due regard should be given to the possible effect of mass as well as to the physical state of the incorporated radionuclide.
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