Gøtzsche P C, Andreasen F, Egsmose C, Lund B
Rheumatological Department, University Hospital, Hvidovre, Denmark.
Scand J Rheumatol. 1988;17(1):11-6. doi: 10.3109/03009748809098754.
The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.
老年风湿性疾病患者和7名健康年轻人口服萘普生（Naprosyn，Syntex公司生产），剂量为500毫克，每日两次，共4周。采用质量碎片分析法测定血清浓度。在给予初始1000毫克剂量后，两组在萘普生的血清峰值浓度、达到血清峰值浓度的时间、血清浓度-时间曲线下面积、分布容积、消除半衰期或全身清除率方面未发现显著差异。在稳态时，老年组萘普生的总谷浓度中位数为50.5毫克/升，年轻组为62.7毫克/升（p = 0.08）；游离浓度分别为58微克/升和44微克/升（p = 0.06）。血清白蛋白与萘普生的游离分数之间存在显著负相关（R = -0.58，p = 0.01）。萘普生的肝提取率相对较低，提示老年人蛋白质结合减少可能掩盖了与年龄相关的细胞活性降低。老年患者的内在清除率估计值降低了37%。建议老年人在萘普生剂量范围的下限开始用药。
