期和药代动力学的研究多药耐药性调制器与时代dexverapamil化疗。

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威尔逊WH Jamis-Dow C,科比G,巴调频,Klecker RW,贝茨,Chabner写英航,斯坦伯格SM,科勒博士,Wittes再保险

期和药代动力学的研究多药耐药性调制器与时代dexverapamil化疗。

8月肿瘤防治杂志。1995;13 (8):1985 - 94。doi: 10.1200 / JCO.1995.13.8.1985。

PubMed ID

7636539 (在PubMed

]

文摘

用途:Dexverapamil 22的竞争性抑制剂(Pgp)外排泵,一个强有力的多药耐药性机制(mdr-1)体外。我们进行了第一阶段的研究来确定最大耐受剂量(MTD)和药物动力学的dexverapamil依托泊苷、强的松、长春新碱、环磷酰胺、阿霉素化疗(时代)。患者和方法:符合条件的患者复发或难治性淋巴瘤或肉瘤。患者最初仅接受时代,和那些有稳定或进行性疾病跨越收到dexverapamil在随后的周期的时代。Dexverapamil是6天的口服药物和升级8个剂量水平从240到1200 mg / m2 / d。药物动力学dexverapamil及其活性代谢物,nor-dexverapamil,得到在大多数病人。阿霉素在七个病人,药物动力学,doxorubicinol,依托泊苷测定时代有或没有dexverapamil成对的周期。结果:六十五名患者接受130次dexverapamil /时代化疗。dexverapamil的MTD 150 mg / m2每4小时(900 mg / m2 / d),和低血压校长dose-limiting毒性。dexverapamil面积曲线(AUC)与dexverapamil剂量增加的比例,但重要interpatient发生变化。 At the MTD, the median plasma average concentrations of dexverapamil and nor-dexverapamil were 1.2 and 1.4 mumol/L, respectively. Dexverapamil did not affect the steady-state concentration (Css) of etoposide, but increased the Css of doxorubicin and doxorubicinol nearly twofold. The absolute neutrophil and platelet nadirs were significantly lower on the dexverapamil cycles compared with cycles of EPOCH alone, but other chemotherapy-related toxicities did not change. CONCLUSION: The phase II recommended dose of dexverapamil with EPOCH is 150 mg/m2 every 4 hours. This dose was well tolerated on an outpatient basis and achieved plasma concentrations of dexverapamil and nor-dexverapamil within the effective range for Pgp inhibition in vitro. Although dexverapamil increased the hematopoietic toxicity of EPOCH, it was mild, readily reversible, and offset by EPOCH dose reductions. Dexverapamil should be considered for further study.

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药物靶点

药物	目标	类	生物	药理作用	行动
Dexverapamil	22 - 1	蛋白质	人类	是的	抑制剂	细节

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Dexverapamil	22 - 1	蛋白质	人类	未知的	抑制剂	细节