BACKGROUND:To assess the pharmacokinetic profile and time-course of trough concentrations and hemoglobin levels associated with subcutaneous weekly administration of epoetin beta in lung cancer patients with chemotherapy-induced anemia. METHODS:Epoetin beta was subcutaneously administered to 15 anemic lung cancer patients once weekly for 8 weeks at doses of 9000, 18,000 and 36,000 IU. Pharmacokinetic parameters (C(max), AUC(inf) and T(1/2)) were determined after the first single dose administration on a model-independent basis, and the relationship between the dose and these parameters was examined for linearity. RESULTS:Weekly administration of epoetin beta at 9000, 18,000 and 36,000 IU produced C(max) values of 308 +/- 117 (mean +/- standard deviation), 678 +/- 86.7 and 1316 +/- 766 mIU/ml, and AUC(inf) values of 15,300 +/- 9524, 54,574 +/- 16,265 and 88,501 +/- 55,687 hr mIU/ml, respectively, showing dose-proportional increases. Trough concentrations tended to increase in the presence of severe bone marrow suppression induced by chemotherapy or other factors. Extremely high values were seen in three patients, but there was no apparent trend toward an increase with repeated doses. After 8 weeks' administration at 9000, 18,000 and 36,000 IU, hemoglobin levels were changed by -0.37 +/- 1.26, 2.15 +/- 1.36 and 2.82 +/- 2.17 g/dl, respectively. CONCLUSIONS:Epoetin beta exhibited linear pharmacokinetics when administered to anemic cancer patients at weekly doses of 9000-36,000 IU and did not cause drug accumulation. Hemoglobin levels increased with weekly doses of 18,000 or 36,000 IU.

译文

背景:为了评估与化疗引起的贫血的肺癌患者每周皮下注射依泊汀β相关的药代动力学特征,谷浓度和血红蛋白水平的时程变化。
方法:Epoetin beta每周一次皮下注射15例贫血性肺癌患者,共9000、18,000和36,000 IU,共8周。在不依赖模型的基础上首次单次给药后确定药代动力学参数(C(max),AUC(inf)和T(1/2)),并检查剂量与这些参数之间的线性关系。
结果:每周以9000、18,000和36,000 IU施用epoetin beta产生的C(max)值为308 /-117(平均值/-标准偏差),678 /-86.7和1316 /-766 mIU / ml和AUC(inf )分别为15,300 /-9524、54,574 /-16,265和88,501 /-55,087 hr mIU / ml,表明剂量成比例增加。在由化学疗法或其他因素引起的严重骨髓抑制的情况下,谷浓度趋于增加。在三名患者中观察到极高的值,但是并没有明显的趋势表明重复剂量会增加。在9000、18,000和36,000 IU给药8周后,血红蛋白水平分别改变了-0.37 /-1.26、2.15 /-1.36和2.82 /-2.17 g / dl。
结论:Epoetinβ每周以9000-36,000 IU的剂量向贫血癌症患者给药时显示出线性的药代动力学,并且不会引起药物蓄积。血红蛋白水平随着每周18,000或36,000 IU的剂量而增加。

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