摘要
目的研究环磷酰胺 (CTX)对丁硫氨酸亚砜胺 (BSO)在SD大鼠体内的药代动力学的影响。 方法SD大鼠腹腔注射CTX 2 0mg/kg(用药组 )或生理盐水 (对照组 ) 4d后 ,静脉注射BSO 2 0 0mg/kg。以邻 -苯二甲醛(OPA)柱前衍生反相HPLC为检测手段 ,测定血浆中BSO的浓度。以 3P87软件对实验数据进行拟合 ,判断房室模型并计算药代动力学参数。 结果SD大鼠静脉注射BSO 2 0 0mg/kg ,体内的动力学过程为二室模型 ,T1/2α为 2 7.4±5 .3min ,T1/2 β为 15 9.3± 10 7.3min ,CLs 为 11.8± 2 .3ml·min-1·kg-1,AUC为 2 99.36± 5 0 .13μg·ml-1·h ;SD大鼠在用CTX后 ,BSO在其体内动力学特征也是二室模型 ,T1/2α为 2 5 .2± 2 .2min ,T1/2 β为 114 .3± 2 5 .9min ,CLs 为 13.8± 3.8ml·min-1·kg-1,AUC为 2 5 6 .5 5± 6 6 .2 8μg·ml-1·h。用药组和对照组的药代动力学参数无显著性差异。结论CTX不影响BSO在大鼠体内的药代动力学过程。
Objective To study the effect of cyclophosphamide(CTX) on the pharmacokinetics of buthionine sulfoximine (BSO) in Sprague-Dawley(SD) rats. Methods SD rats were treated with saline or CTX in saline(20mg/kg) ip for 4d, and then received BSO 200mg/kg iv. The BSO concentration in rat plasma was determined by a reverse phase HPLC with fluorescence detection after precolumn derivatization with o-phthaldialdehyde. The data were processed with the 3P87 software to determine the compartment model and the pharmacokinetic parameters. Results A single intravenous dose of BSO 200mg/kg was eliminated from plasma in a two-compartment manner in SD rats. The pharmacokinetic parameters of BSO were as follows:in control rats, T 1/2α =27.4±5.3min, T 1/2β =159.3±107.3min, AUC=299.36±50.13μg·ml -1 ·h,CL s=11.8±2.3ml·min -1 ·kg -1 ; in CTX-treated rats, T 1/2α =25.2±2.2min,T 1/2β =114.3±25.9min, CL s=13.8±3.8ml·min -1 ·kg -1 , AUC= 256.55 +66.28μg·ml -1 ·h. Conclusion There was no significant difference between the pharmacokinetic parameters of control and CTX-treated SD rats.
出处
《上海第二医科大学学报》
CSCD
2002年第2期121-123,139,共4页
Acta Universitatis Medicinalis Secondae Shanghai
