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

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 ) ,其余各参数差异无显著性

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

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 .