Kurowski M
Int J Clin Pharmacol Res. 1985;5(4):255-63.
Twenty patients suffering from osteoarthritis or rheumatoid arthritis, aged between 60 and 85 years, received 200 mg indoprofen tablets thrice daily for 4-7 days. Following the last dose, plasma samples were drawn and analysed for indoprofen. The mean peak plasma concentration of 25.5 +/- 7.06 micrograms/ml indoprofen was reached after 1.25 +/- 0.71 h. The total area under the curve was calculated as 207.2 +/- 108.7 micrograms X h/ml. Indoprofen was eliminated with a mean elimination half-life of t1/2 beta = 8.29 +/- 2.93 h compared with 5.5 +/- 0.64 h in young subjects. In elderly patients receiving indoprofen, terminal plasma half-lives and area under the plasma level time curves corrected for body weight were moderately increased compared with young subjects whereas no significant differences were found for Vd beta. During the dosage interval indoprofen levels were appreciably higher in elderly patients than in healthy volunteers due to higher nadir values and slower elimination half-lives, whereas only minor differences could be detected for peak plasma levels. The differences observed between young healthy volunteers and elderly patients may be explained by the reduction of renal function with increasing age, since creatinine clearance was 30-40% lower than normal values. The dose schedule for elderly patients over 60 years of age should therefore be adjusted to 200 mg indoprofen twice daily. A further reduction of the total daily dose should be considered for patients suffering from renal diseases associated with reduced creatinine clearance.
20名年龄在60至85岁之间的骨关节炎或类风湿关节炎患者,每日三次服用200毫克吲哚美辛片,持续4至7天。在最后一剂服药后,采集血浆样本并分析其中的吲哚美辛。服药后1.25±0.71小时达到吲哚美辛的平均血浆峰值浓度25.5±7.06微克/毫升。曲线下总面积计算为207.2±108.7微克·小时/毫升。吲哚美辛的消除平均半衰期为t1/2β=8.29±2.93小时,而年轻受试者为5.5±0.64小时。在接受吲哚美辛治疗的老年患者中,校正体重后的终末血浆半衰期和血浆水平时间曲线下面积与年轻受试者相比适度增加,而Vdβ未发现显著差异。在给药间隔期间,由于较低的最低点值和较慢的消除半衰期,老年患者的吲哚美辛水平明显高于健康志愿者,而血浆峰值水平仅检测到微小差异。年轻健康志愿者和老年患者之间观察到的差异可能是由于肾功能随年龄增长而降低,因为肌酐清除率比正常值低30 - 40%。因此,60岁以上老年患者的给药方案应调整为每日两次服用200毫克吲哚美辛。对于患有与肌酐清除率降低相关的肾脏疾病的患者,应考虑进一步降低每日总剂量。