Day R O, Furst D E, Dromgoole S H, Kamm B, Roe R, Paulus H E
Clin Pharmacol Ther. 1982 Jun;31(6):733-40. doi: 10.1038/clpt.1982.103.
Twenty-four patients with rheumatoid arthritis were tested in a randomized, double-blind. Latin-square comparison of 250, 750 and 1500 mg of naproxen daily. Each received each dose for 2 wk and baseline disease activity was established during withdrawal of medication before and after the study. Nine standard measures of efficacy were tested at each evaluation. No order effect or change in baseline was found. Total and unbound naproxen concentrations were measured by high-pressure liquid chromatography and equilibrium dialysis, respectively. A linear dose-response relationship (P less than 0.05) was demonstrated between naproxen and joint count, patient's pain assessment, activities of daily living index, physician's global assessment, and grip strength. The relationship to patients' global assessment was of uncertain significance (P less than 0.07). A positive dose to serum level correlation (1, 2, and 12 hr after dose) was apparent (r greater than 0.78). When patients were defined as responders or nonresponders by a summed efficacy score, there was a serum concentration-response relationship; the percentage of responding patients increased with each serum level quartile: 25%, 31%, 59%, and 75%. Patients with a trough total serum naproxen concentration under 18 micrograms/ml did not respond, while 76% of patients with trough total serum concentrations above 50 micrograms/ml responded. No serum naproxen toxicity level relationship was established.
对24例类风湿性关节炎患者进行了一项随机、双盲、拉丁方试验，比较每日服用250毫克、750毫克和1500毫克萘普生的疗效。每位患者每种剂量服用2周，在研究前后停药期间确定基线疾病活动度。每次评估时测试9项标准疗效指标。未发现顺序效应或基线变化。分别通过高压液相色谱法和平衡透析法测量萘普生的总浓度和游离浓度。萘普生与关节计数、患者疼痛评估、日常生活活动指数、医生整体评估和握力之间呈现线性剂量反应关系（P<0.05）。与患者整体评估的关系意义不确定（P<0.07）。给药后1小时、2小时和12小时，剂量与血清水平呈明显正相关（r>0.78）。当根据综合疗效评分将患者定义为反应者或无反应者时，存在血清浓度反应关系；随着血清水平四分位数的增加，有反应患者的百分比增加：25%、31%、59%和75%。血清萘普生谷浓度低于18微克/毫升的患者无反应，而血清萘普生谷浓度高于50微克/毫升的患者中有76%有反应。未确定血清萘普生毒性水平关系。
