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 200mg·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.