环磷酰胺对丁硫氨酸亚砜胺在Walker-256荷瘤大鼠体内的药代动力学的影响  

Effects of cyclophosphamide on pharmacokinetics of buthionine sulfoximine in Walker-256 tumor-bearing rats

作　　者：范春玲[1] 李端[2] 

机构地区：[1]上海第二医科大学附属瑞金医院.上海市高血压研究所,上海200025 [2]复旦大学药学院药理学教研室,上海200032

出　　处：《中国药理学通报》2002年第2期229-232,共4页Chinese Pharmacological Bulletin

摘　　要：目的　研究环磷酰胺 (CTX)对化疗增敏剂丁硫氨酸亚砜胺 (BSO)在Walker 2 5 6荷瘤大鼠体内的药代动力学的影响。方法　Walker 2 5 6荷瘤大鼠ipCTX 2 0mg·kg-1或生理盐水 4d后 ,ivBSO 2 0 0mg·kg-1。以邻 苯二甲醛柱前衍生反相HPLC为检测手段 ,测定血浆中BSO的浓度 ,以 3P87对实验数据进行拟合 ,计算药代动力学参数。结果　荷瘤大鼠静脉注射BSO 2 0 0mg·kg-1,体内的动力学过程为二室模型 ,T1/ 2α为 (11 1± 2 4 )min ,T1/ 2 β为 (6 5± 14 )min ,CLs为(12 8± 1 3)ml·min-1·kg-1,AUC为 (2 6 2± 2 6 )mg·L-1·h ;BSO在CTX治疗组荷瘤大鼠体内的动力学特征也是二室模型 ,T1/ 2α为 (8 2± 1 8)min ;T1/ 2 β为 (42± 3)min ;CLs为 (13 4± 1 9)ml·min-1·kg-1,AUC为 (2 5 2± 35 )mg·L-1·h。结论　CTX治疗组与对照组相比 ,用药组BSO的消除显著快于未经CTX治疗的大鼠 (P <0 0 5 ) 。AIM To study the effects of cyclophosphamide (CTX) on the pharmacokinetics of buthionine sulfoximine (BSO)in Walker 256 tumor bearing rats. METHODS Walker 256 tumor bearing rats were treated ip for 4 days with saline or CTX in saline (20 mg·kg -1 ), then received iv BSO 200 mg·kg -1 . BSO concentration in rat plasma was determined by a reverse phase HPLC with fluorescence detection after precolumn derivatization with o phthaldialdehyde. Compartment model and pharmacokinetic parameters were determined by 3P87 software processed on a computer. RESULTS A single intravenous dose of BSO 200 mg·kg -1 was eliminated from plasma in a two compartment manner in tumor bearing rats. The pharmacokinetic parameters of BSO were as follows: In tumor bearing control rats, T 1/2α =(11 1±2 4) min, T 1/2β =(65±14) min, CLs=(12 8±1 3) ml·min -1 ·kg -1 , AUC=(262±26) mg·L -1 ·h; in tumor bearing CTX treated rats, T 1/2α =(8 2±1 8) min, T 1/2β =(42±3) min, CLs=(13 4±1 9) ml·min -1 ·kg -1 ,AUC=(252±35) mg ·L -1 ·h. CONCLUSION There is no significant difference between the parameters of tumor bearing control and CTX treated rats except T 1/2β .

关 键 词：丁硫氨酸亚砜胺 环磷酰胺 药代动力学 高效液相色谱法 

分 类 号：R979.1[医药卫生—药品] R73－354[医药卫生—药学]