A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients
A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients
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泼尼莫司汀与泼尼松龙联合苯丁酸氮芥在癌症患者中的药代动力学研究
DOI：
10.1007/bf00685510
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发表时间：
2004
影响因子：
3
通讯作者：
H. Mouridsen
中科院分区：
文献类型：
--
作者：
L. Bastholt;C. Johansson;P. Pfeiffer;L. Svensson;S. Johansson;P. Gunnarsson;H. Mouridsen
本文研究了泼尼松龙和苯丁酸氮芥及其β-氧化代谢产物苯乙酸氮芥（PAM）在大鼠口服泼尼松200 mg和泼尼松龙加苯丁酸氮芥20 mg后的血浆药代动力学特征。共有12名癌症患者完成了这项试验。药物在交叉研究中以单剂量给药，并收集连续32 h的血浆样品。苯丁酸氮芥和PAM测定气相色谱/质谱法和泼尼松龙，放射免疫分析法。泼尼松龙和苯丁酸氮芥部分的中位相对利用度分别为19%和16%。与苯丁酸氮芥和泼尼松龙的混合物相比，泼尼松龙以及苯丁酸氮芥和PAM在用泼尼松碱治疗后出现较晚并且在血浆中的浓度显著较低。我们还发现，与苯丁酸氮芥本身相比，给予泼尼松后，苯丁酸氮芥和PAM在血浆中的消除相延长。相比之下，泼尼松龙部分的泼尼松木司汀的消除和普通泼尼松龙片剂给药后的消除似乎没有差异。泼尼松给药后烷基化组分的血浆曲线改变可能对泼尼松的临床疗效很重要。
SummaryThe pharmacokinetic characteristics of prednisolone and of chlorambucil and its β-oxidized metabolite, phenylacetic mustard (PAM) were studied in plasma after the oral administration of 200 mg prednimustine (Sterecyt) and a regimen consisting of 20 mg prednisolone plus 20 mg chlorambucil, respectively. A total of 12 cancer patients completed this trial. The drugs were given in a cross-over study as single doses, and serial plasma samples were collected for 32 h. Chlorambucil and PAM were assayed by a gas chromatographic/mass spectrometry method and prednisolone, by radioimmunoassay. The median relative availability of the prednisolone and chlorambucil moiety in prednimustine was 19% and 16%, respectively. Prednisolone, as well as chlorambucil and PAM, appeared later and at a significantly lower concentration in plasma after treatment with prednimustine as compared with the mixture of chlorambucil and prednisolone. We also found that the elimination phase of chlorambucil and PAM in plasma is prolonged after the administration of prednimustine as compared with chlorambucil per se. In contrast, the elimination of the prednisolone moiety of prednimustine and that following the administration of a plain prednisolone tablet did not seem to differ. The modified plasma profile of the alkylating components following prednimustine administration may be important for the clinical efficacy of prednimustine.