STUDIES ON THE PHARMACOKINETICS OF CHLORAMBUCIL AND PREDNIMUSTINE IN PATIENTS USING A NEW HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY
STUDIES ON THE PHARMACOKINETICS OF CHLORAMBUCIL AND PREDNIMUSTINE IN PATIENTS USING A NEW HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY
复制标题
DOI：
10.1007/bf00451643
复制
发表时间：
1989-01-01
影响因子：
3
通讯作者：
MUHLENBRUCH, B
中科院分区：
文献类型：
--
作者：
OPPITZ, MM;MUSCH, E;MUHLENBRUCH, B
在给患者口服苯丁酸氮芥/泼尼松龙或泼尼莫司汀后，使用新的高效液相色谱（HPLC）测定法测量游离苯丁酸氮芥和苯乙酸芥（苯丁酸氮芥的β-氧化产物）的血浆水平。该测定允许同时检测所分析的化合物，检测下限为 30 ng/ml。发现当给予泼尼莫司汀时，苯丁酸氮芥和苯乙酸芥的药代动力学与其成分苯丁酸氮芥和泼尼松龙一起给药时完全不同。摄入缀合物后，苯丁酸氮芥和苯乙酸芥的血浆浓度-时间曲线与施用各成分后获得的血浆浓度-时间曲线相比显示出“延迟”模式。泼尼莫司汀衍生的苯丁酸氮芥和苯乙酸芥的浓度-时间曲线下平均面积 (AUC) 分别是化学计量等效剂量苯丁酸氮芥后获得的面积的 25% 和 40%。 任何时候都无法检测到游离血浆泼尼莫司汀。这种不同的药代动力学行为可能为临床研究证明的泼尼莫司汀优越的治疗效果提供了解释。
Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the .beta.-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednislone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects prednimustine demonstrated by clinical studies.