Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation

The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT, Patients received busulphan at a dose of either 16 mg/kg wi th cyclophosphamide and ATG (Group A) or 600 mg/m(2) (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days, Busulphan leve ls were analyzed by a modified GC-MS method. The dose of busulphan/kg for p atients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUG, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13, There was no significa nt difference in Vd/F, T1/2 and Kel between the two groups. A significant d ecrease in AUC and Css was found between 1st and 13th doses in group B, but not in group A. The Cl/F values in group A were significantly higher than those in group B after dose 1, but not after dose 13, No increase in toxici ty due to the higher dose of busulphan was noted. We conclude that busulpha n at 600 mg/m(2) results in much higher systemic exposure to the drug as co mpared to 16 mg/kg, without increase in toxicity in children with beta thal assaemia major.