troxacitabine群体药物动力学,小说二氧戊环核苷类似物。

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李CK, Rowinsky EK,李J,贾尔斯F,摩尔MJ,伊达尔戈M, Capparelli E, Jolivet J,贝克SD

troxacitabine群体药物动力学,小说二氧戊环核苷类似物。

癌症研究杂志2006年4月1;12 (7 Pt - 1): 2158 - 65。

PubMed ID

16609029 (在PubMed

]

文摘

目的:开发和验证troxacitabine群体药代动力学模型,一种新型l-nucleoside模拟,由短注入;协变量描述临床影响药代动力学的变化;并设计一个剂量率连续输液管理,以实现微摩尔的浓度较低,这可能是更有效的比短的注入。实验设计:血浆样本111名癌症患者接受troxacitabine(0.12 - -12.5毫克/米(2))作为一个30分钟的注入在第一阶段试验被用来与NONMEM发展模型。临床评估包括肌酐清除率,反是身体表面积,年龄和性别。从模型中,troxacitabine剂量率2.0 - 3.0毫克/米(2)/ d预计将达到一个目标浓度的0.1 micromol / L;等离子体注入期间获取的样本从8个病人接受troxacitabine为期3天的输液。结果:Troxacitabine药物动力学特征是three-compartment线性模型。系统性的平均值间隙(个人间变异性(CV %))从covariate-free模型为9.1 L / h (28%)。肌酐清除率和身体表面积占主体间间隙的变化的36%。 Troxacitabine 2.0 mg/m(2)/d (n = 3) and 3.0 mg/m(2)/d (n = 5) for 3 days produced mean +/- SD end of infusion concentrations of 0.12 +/- 0.03 and 0.15 +/- 0.03 micromol/L, respectively. CONCLUSIONS: Renal function and body surface area were identified as sources of troxacitabine pharmacokinetic variability. The population pharmacokinetic model model-derived dosage rates for continuous infusion administration successfully achieved predetermined target plasma concentrations. The present model may be used to optimize treatment with troxacitabine by developing a dosing strategy based on both renal function and body size.

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药物

Troxacitabine