Analgesic Action of a Sustained Release Preparation of Diclofenac Sodium in a Canine Urate-Induced Gonarthritis

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Using hard capsules (SR318B) developed as a sustained release diclofenac sodium (DF-Na) preparation for once-daily administration, we investigated the persistence of the analgesic effect after oral administration in the canine urate-induced gonarthritis model. In the control group, injection of 2% urate into the knee joint induced gait disorder due to pain 2 hr after administration and thereafter. Gait disorder peaked 6 hr after urate injection, and gradually recovered after 12 hr. In the treatment group, SR318B at 1.0mg DF-Na/kg body weight was orally administered 6 hr before urate injection, and the walking score significantly decreased 2 hr after urate injection compared with the control group (p<0.05). Although the analgesic effect was not observed at the peak of urate-induced pain, the walking score significantly decreased 14, 16, and 18 hr after urate injection compared with the control group (p<0.05). The plasma diclofenac (DF) concentration peaked 6 hr after SR318B administration, and decreased to about 1/3-1/5 12-18 hr after administration (peak of urate-induced pain), and the plasma level was below the quantification limit in three of five animals 24 hr after administration. DF was detected in the synovial fluid 24 hr after administration in all animals and the concentration was 0.03 ± 0.01 μg/ml (mean ± standard error). The above findings showed that the SR318B exhibits a persistent analgesic effect in a canine urate-induced gonarthritis model. Not only DF in the plasma but also the DF that transferred to the synovial fluid may be involved in this persistent analgesic effect.
公益社団法人日本薬学会の論文
2001-10-01

Analgesic Action of a Sustained Release Preparation of Diclofenac Sodium in a Canine Urate-Induced Gonarthritis

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