Effect of Cyclophosphamide on Busulfan Pharmacokinetics and Serum GST Activity in Beagle Dogs

OBJECTIVE To study the effect of cyclophosphamide (Cy) on busulfan (Bu) pharmacokinetics and glutathione S-transferase (GST) activity. METHODS Three beagle dogs were taken for a two-cycle crossover test,and the groups were divided into the control group and the experimental group.The control group was injected Bu alone (0.898 mg·kg^–1).The experimental group was oral Cy (14.960 mg·kg^–1) for 4 consecutive days,firstly,and then injected Bu (0.898 mg·kg^–1).The 2 mL of blood samples were collected from the forelimb veins of dogs at 0.083,0.25,0.5,0.75,1,1.5,2,3,4,6,8 h.The Bu concentration was determined by HPLC,and the pharmacokinetic parameters were calculated using a non-compartment model.The GST activity of the control group and the experimental group was measured by UV spectrophotometry and compared.RESULTS Compared with the control group,the MRT and AUC_0-t of Bu in the experimental group decreased by 25.2% and 44.5%,respectively.There was a statistically significant difference (P<0.05).The results of GST activity showed that the GST activity in the experimental group was higher than that of the control group at each time points.CONCLUSION GST activity increased after pre-administration of Cy,Bu elimination accelerated,and the overall level of blood concentration decreased.