Effects of cyclophosphamide on pharmacokinetics of buthionine sulfoximine in Walker-256 tumor-bearing rats / 中国药理学通报

ABSTRACT

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 1/2? =(11 1?2 4) min, T 1/2? =(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 1/2? =(8 2?1 8) min, T 1/2? =(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 1/2? .