Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.
Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.
复制标题
阿糖胞苷在急性髓系白血病患者中的药代动力学。
DOI：
10.1111/j.1365-2125.1979.tb01005.x
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发表时间：
1979
影响因子：
3.4
通讯作者：
D. Grahame
中科院分区：
文献类型：
--
作者：
A. Harris;C. Potter;C. Bunch;J. Boutagy;D. Harvey;D. Grahame
1单次静注阿糖胞苷后的药代动力学研究。初诊AML患者单次静脉推注2 mg/kg Ara-C，采用生物测定法和GC-MS法测定血药浓度。2多数患者的血药浓度随时间呈双相或三相下降。GC-MS法测得血浆清除率为3.90~18.1Min，终末半衰期为7~107min。3气质联用法与生物法相关性较差，可能是由于Ara-C后成纤维细胞释放内源核苷干扰了生物法。4用气相色谱-质谱法测定14例患者持续输液过程中的血药浓度。血浆清除量明显低于给药后的0.39~5.25 L/分钟。5根据输注剂量、清除量和输注时间计算，反应(外周血细胞计数的缓解或下降)与暴露于Ara-C之间没有相关性。6这项研究表明，不同患者的Ara-C药代动力学明显不同，而且与治疗反应相关的血药浓度范围很大。
1 The pharmacokinetics of cytosine arabinoside were studied after a single i.v. bolus of 2 mg/kg ara-C in patients with newly diagnosed untreated AML, using a bioassay and GC-MS method to measure the plasma concentrations. 2 Most patients showed a bi- or tri-phasic decline in plasma concentrations with time. Plasma clearance was 3.9 to 18.1 l/min as measured by the GC-MS method, and terminal half-lives varied from 7--107 min. 3 There was poor correlation of the GC-MS assay with the bioassay, probably because the latter was interfered with by the release of endogenous nucleosides from blasts after after ara-C. 4 Plasma concentrations were measured by GC-MS during continuous infusions in 14 patients. Plasma clearances were much lower than after a bolus, 0.39 to 5.25 l/min. 5 There was no correlation of response (remission or fall in peripheral blast count) with exposure to ara-C calculated from infusion dose, clearance and duration of infusion. 6 This study shows that ara-C pharmacokinetics varies markedly from patient to patient and that there is a wide range in the plasma concentrations associated with therapeutic response.