Cuzzolin L, Conforti A, Adami A, Lussignoli S, Menestrina F, Del Soldato P, Benoni G
Institute of Pharmacology, University of Verona, Italy.
Pharmacol Res. 1995 Jan;31(1):61-5. doi: 10.1016/1043-6618(95)80049-2.
Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.
在角叉菜胶水肿模型中，比较了萘普生及其衍生物硝萘普生5和10毫克/千克剂量的急性抗炎疗效以及对大鼠的胃肠道毒性。此外，在佐剂性关节炎中评估了这两种药物的作用，经口给予4和8毫克/千克的慢性剂量，持续18天。硝萘普生使水肿减轻的持续时间更长（直至5小时）；两种受试药物剂量对关节炎的抑制率均达到50%或更高。从胃的组织学检查来看，在用萘普生治疗的一些大鼠中观察到广泛的黏膜血管充血和出血性病变。萘普生6和18毫克/千克以及硝萘普生54毫克/千克处理的动物溃疡发生率分别为50%、100%和10%。与萘普生相比，在用硝萘普生治疗的关节炎和水肿大鼠中观察到更好的胃肠道耐受性：这可能是由于一氧化氮的存在，其作用是维持组织灌注和完整性。
