Dunagan F M, McGill P E, Kelman A W, Whiting B
Department of Materia Medica, Stobhill General Hospital, Glasgow, UK.
Br J Rheumatol. 1988 Feb;27(1):48-53. doi: 10.1093/rheumatology/27.1.48.
Information on the relationship between the plasma concentration of nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical response in rheumatoid arthritis is sparse. As a result treatment is often relatively empirical. Standard doses are prescribed and an apparent lack of response leads either to the prescription of another drug, or an increase in the dose beyond that recommended. This study investigated 18 patients given three doses (500, 1000 and 1500 mg/day) of naproxen in a randomized double-blind design for 12 days at a time. Using a linear modelling approach we found that three out of four clinical response measurements improved linearly with increasing naproxen trough concentrations, suggesting that most patients will achieve an improvement in symptoms if the dose of naproxen is increased up to 1500 mg/day. However, since trough naproxen concentrations show a less than proportional increase with increasing dose (due to saturation of binding sites on plasma albumin), the improvement in response will be less dramatic as the dose is increased.
关于非甾体抗炎药（NSAIDs）血浆浓度与类风湿性关节炎临床反应之间关系的信息较为匮乏。因此，治疗往往相对缺乏依据。通常会开出标准剂量的药物，而明显缺乏疗效则会导致要么换用另一种药物，要么将剂量增加至超出推荐剂量。本研究采用随机双盲设计，让18名患者每次服用三种剂量（500、1000和1500毫克/天）的萘普生，为期12天。使用线性建模方法，我们发现四项临床反应测量指标中有三项随着萘普生谷浓度的升高呈线性改善，这表明如果将萘普生剂量增加至1500毫克/天，大多数患者的症状将会得到改善。然而，由于萘普生谷浓度随剂量增加的增幅小于剂量增加的比例（由于血浆白蛋白上结合位点的饱和），随着剂量的增加，反应的改善程度将不会那么显著。
