Ekstrand R, Alván G, Magnusson A, Oliw E, Palmér L, Rane A
Scand J Rheumatol. 1981;10(2):69-75. doi: 10.3109/03009748109095275.
Twelve rheumatic patients were given 2.0 and 4.5 g acetylsalicylic acid daily in two 3-week periods. On days 13 and 20 of each period the patients took a suppository containing either placebo or 50 mg of indomethacin. The study was performed double-blind. Indomethacin had a significant additive effect during ASA therapy with 2 g daily as estimated by articular index and subjective ratings of pain and morning stiffness. On the 4.5 g ASA dose there was a significant improvement only for articular index. The patients experienced less pain during maintenance therapy with 4.5 g of ASA compared with 2.0 g daily. Both ASA doses induced complete inhibition of prostaglandin PGF2 alpha release from platelets. Thus the suppression of PGF2 alpha release does not reflect the therapeutic response of these drugs. Side effects observed comprised tinnitus, dizziness and gastritis. In 2 of the patients the aminotransferase levels increased, indicating hepatotoxicity. The protein binding of salicylate decreased with increasing salicylate concentration. As the dose was increased from 2.0 to 4.5 g/day the unbound concentration increased 5 to 24 times. This reflects the combined effect of capacity-limited metabolism and capacity-limited protein binding of salicylate.
12名风湿患者在两个为期3周的阶段中，每日分别服用2.0克和4.5克乙酰水杨酸。在每个阶段的第13天和第20天，患者使用含有安慰剂或50毫克吲哚美辛的栓剂。该研究采用双盲法进行。根据关节指数以及疼痛和晨僵的主观评分估计，吲哚美辛在每日2克乙酰水杨酸治疗期间具有显著的相加作用。在4.5克乙酰水杨酸剂量时，仅关节指数有显著改善。与每日2.0克相比，患者在每日4.5克乙酰水杨酸维持治疗期间疼痛减轻。两种乙酰水杨酸剂量均能完全抑制血小板释放前列腺素PGF2α。因此，PGF2α释放的抑制并不反映这些药物的治疗反应。观察到的副作用包括耳鸣、头晕和胃炎。2名患者的转氨酶水平升高，表明存在肝毒性。随着水杨酸盐浓度的增加，水杨酸盐的蛋白结合率降低。当剂量从2.0克/天增加到4.5克/天时，游离浓度增加了5至24倍。这反映了水杨酸盐容量限制代谢和容量限制蛋白结合的综合作用。
