Engelhardt G, Homma D, Schnitzler C
Department of Pharmacological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Inflamm Res. 1995 Dec;44(12):548-55. doi: 10.1007/BF01757360.
The effects of meloxicam, piroxicam, diclofenac and tenidap on the swelling of hind paws, radiologically-detectable bone and cartilage destruction of hind paws, increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition in male Lewis rats with adjuvant arthritis were studied following once-daily oral administration of these drugs for 21 days. All the drugs dose-dependently inhibited hind paw swelling. For equal activity against hind paw swelling caused by the secondary reaction, the required daily dose of piroxicam was about twice that of meloxicam; those of diclofenac and tenidap were about 3.5 and 60 times higher respectively. The bone and cartilage destruction induced by adjuvant arthritis were inhibited by meloxicam at low daily doses and by piroxicam at doses approximately four times those of meloxicam. Diclofenac and tenidap had only a weak effect on radiologically-detectable lesions when administered at doses sufficient to reduce paw swelling. Meloxicam also had a dose-dependent corrective effect on the systemic changes which occur in adjuvant arthritic rats, e.g. increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition. Piroxicam produced similar effects, at 3-4 times higher doses. Diclofenac and tenidap did not show comparable effects when administered at appropriate doses. These findings indicate that the action of meloxicam and piroxicam differs from that of diclofenac and tenidap in adjuvant arthritis in the Lewis rat. At oral doses which significantly reduce edema formation, only meloxicam and piroxicam showed a significant effect on systemic parameters of adjuvant disease in the Lewis rat.
在雄性Lewis佐剂性关节炎大鼠中,研究了美洛昔康、吡罗昔康、双氯芬酸和替硝唑对后爪肿胀、后爪放射学可检测到的骨和软骨破坏、脾脏重量增加、红细胞沉降率升高以及血清蛋白组成变化的影响。这些药物每日口服一次,持续21天。所有药物均剂量依赖性地抑制后爪肿胀。对于抑制由继发性反应引起的后爪肿胀具有同等活性而言,吡罗昔康的每日所需剂量约为美洛昔康的两倍;双氯芬酸和替硝唑的每日所需剂量分别约高3.5倍和60倍。美洛昔康在低剂量时可抑制佐剂性关节炎诱导的骨和软骨破坏,吡罗昔康的有效剂量约为美洛昔康的四倍。双氯芬酸和替硝唑在给予足以减轻爪肿胀的剂量时,对放射学可检测到的病变仅有微弱作用。美洛昔康对佐剂性关节炎大鼠出现的全身变化,如脾脏重量增加、红细胞沉降率升高和血清蛋白组成变化,也有剂量依赖性的纠正作用。吡罗昔康在3 - 4倍高的剂量时产生类似作用。双氯芬酸和替硝唑在给予适当剂量时未显示出类似作用。这些发现表明,在Lewis大鼠佐剂性关节炎中,美洛昔康和吡罗昔康的作用不同于双氯芬酸和替硝唑。在显著减少水肿形成的口服剂量下,只有美洛昔康和吡罗昔康对Lewis大鼠佐剂性疾病的全身参数有显著影响。