Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833
Changes in doxorubicin distribution and toxicity in mice pretreated with the cyclosporin analogue SDZ PSC 833
复制标题
用环孢菌素类似物 SDZ PSC 833 预处理的小鼠中阿霉素分布和毒性的变化
DOI：
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发表时间：
1995
影响因子：
3
通讯作者：
M. D’Incalci
中科院分区：
文献类型：
--
作者：
O. Gonzalez;T. Colombo;M. Fusco;L. Imperatori;M. Zucchetti;M. D’Incalci
SdZ PSC 833(PSC 833)是一种环孢素A类似物，正在进行临床研究，与阿霉素(Dx)或其他抗癌药物联合作为1型多药耐药(MDR-1)逆转剂。本研究旨在研究PSC-833对Dx在非荷瘤CDF1雄性小鼠体内分布和毒性的影响。给小鼠灌胃PSC 833 ip。在静脉注射前30分钟。DX治疗。用高效液相色谱法测定小鼠血清、心、肠、肝、肾和肾上腺中Dx在72小时内的含量。在所有组织中，10 mg/kg Dx与12.5 mg/kg PSC 833或25 mg/kg PSC 833联用的小鼠的Dx浓度-时间曲线下面积(AUC)值明显大于单独接受Dx的小鼠。Dx在肠、肝、肾和肾上腺中的浓度升高幅度最大。心脏方面的差异较小，尽管差异很大。PSC 833似乎对尿液或粪便中Dx的排泄或Dx代谢没有很大影响。无任何毒性的PSC 833剂量显著增强了Dx的急性和延迟毒性。这种增强毒性的机制尚未阐明，但很可能与PSC 833抑制P-糖蛋白(Pgp)泵而增加Dx的组织滞留有关，就像最近对环孢素A提出的那样。
SDZ PSC 833 (PSC 833) is a cyclosporin A analogue that is under clinical investigation in combination with doxorubicin (Dx) or other anticancer agents as a type-1 multidrug resistance (MDR-1)-reversing agent. The present study was focused on the effects of PSC 833 on the distribution and toxicity of Dx in non-tumor-bearing CDF1 male mice. Mice were given PSC 833 i.p. at 30 min before i.v. Dx treatment. Dx levels were determined by a high-performance liquid chromatography (HPLC) assay at different times during a 72-h period following Dx treatment in the serum, heart, intestine, liver, kidney, and adrenals of mice. In all tissues, Dx area under the concentrationtime curve (AUC) values were much greater in mice receiving 10 mg/kg Dx in combination with 12.5 or 25 mg/kg PSC 833 than in mice receiving Dx alone. The highest increase in Dx concentrations was found in the intestine, liver, kidney, and adrenals. Lower, albeit significant, differences were found in the heart. PSC 833 did not appear to influence either urinary or fecal Dx elimination or Dx metabolism to a great extent. Doses of PSC 833 devoid of any toxicity potentiated the acute and delayed toxicity of Dx dramatically. The mechanism responsible for this enhanced toxicity has not yet been elucidated but is likely to be related to an increased tissue retention of Dx due to inhibition of the P-glycoprotein (Pgp) pump by PSC 833, as has recently been proposed for cyclosporin A.
影响因子：
21.1
作者：
J. M. Ford;W. Hait
通讯作者：
J. M. Ford;W. Hait
DOI：
10.1200/jco.1992.10.10.1624
发表时间：
1992-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
A. Yahanda;K. M. Alder;G. Fisher;N. Brophy;J. Halsey;R. Hardy;M. Gosland;B. Lum;B. Sikic
通讯作者：
A. Yahanda;K. M. Alder;G. Fisher;N. Brophy;J. Halsey;R. Hardy;M. Gosland;B. Lum;B. Sikic
影响因子：
45.3
作者：
BARTLETT, NL;LUM, BL;SIKIC, BI
通讯作者：
SIKIC, BI