Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation.
Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation.
复制标题
类风湿关节炎患者活动性多关节炎症期间萘普生的药代动力学。
DOI：
10.1111/j.1365-2125.1987.tb03028.x
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发表时间：
1987
影响因子：
3.4
通讯作者：
F. Gribnau
中科院分区：
文献类型：
--
作者：
F. A. van den Ouweland;M. Franssen;L. V. D. van de Putte;Y. Tan;C. V. van Ginneken;F. Gribnau
类风湿性关节炎患者常伴有低白蛋白血症，这是疾病活动的一个标志。鉴于萘普生与白蛋白的广泛结合，在8名患者和8名健康男性志愿者中研究了每日两次500 mg长期摄入期间总药物和未结合药物的药代动力学。在一个给药间隔期间，总萘普生的血清浓度-时间曲线下面积，AUC（0，12），患者（641 +/- 101 mg l-1 h）小于志愿者（896 +/- 85 mg l-1 h; P <0.0001）。患者的未结合萘普生AUCu（0，12）（1.9 +/- 0.9 mg l-1 h）大于志愿者（0.7 +/- 0.2 mg l-1 h; P <0.01）。患者中较高的未结合的萘普生浓度伴随着表观清除率/生物利用度（CL/F）增加约40%和分布容积（V/F）增加60%。CL/F和V/F均与个体血清白蛋白浓度呈负相关（分别为r = 0.76，P <0.001; r =-0.85，P <0.001）。目前尚不清楚活动性类风湿性关节炎和伴随的低白蛋白血症患者血清中的高未结合萘普生浓度是否伴随副作用增加，如果抗炎作用与未结合药物浓度相关，则可能有益。
Patients with rheumatoid arthritis often have hypoalbuminaemia as a sign of disease activity. In view of the extensive binding of naproxen to albumin, the pharmacokinetics of total and unbound drug were studied in eight patients and eight healthy male volunteers during chronic intake of 500 mg twice daily. The area under the serum concentration-time curve of total naproxen during a dose interval, AUC (0,12), smaller in patients (641 +/- 101 mg l-1 h) than in volunteers (896 +/- 85 mg l-1 h; P less than 0.0001). The unbound naproxen AUCu (0,12) was larger in patients (1.9 +/- 0.9 mg l-1 h) than in volunteers (0.7 +/- 0.2 mg l-1 h; P less than 0.01). The higher unbound naproxen concentrations in patients were accompanied by an approximately 40% increase in apparent clearance/bioavailability (CL/F) and a 60% increase in volume of distribution (V/F). Both CL/F and V/F were inversely correlated with the individual serum albumin concentration (r = 0.76, P less than 0.001; r = -0.85, P less than 0.001, respectively). The high unbound naproxen concentration in the serum of patients with active rheumatoid arthritis and concomitant hypoalbuminaemia is not known to be accompanied by an increase in side effects and may be beneficial if anti-inflammatory effects correlate with unbound drug concentration.