TY - JOUR
T1 - Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation
AU - Poonkuzhali, B.
AU - Srivastava, A.
AU - Quernin, M. H.
AU - Dennison, D.
AU - Aigrain, E. J.
AU - Kanagasabapathy, A. S.
AU - Krishnamoorthy, R.
AU - Chandy, M.
N1 - Funding Information:
This study was supported in part by the Indian Council of Medical Research grant towards the project ‘Advanced Center for Bone Marrow Transplantation for Thalassaemia in India’ (56/2/93-BMS II) and the Indo-French research project (Grant No. 94NS4) attributed to Dr R Krishnamoorthy of INSERM U458, Paris, France. Our special thanks to the BMT unit nursing staff for their assistance in blood sample collection for busulphan analysis.
PY - 1999
Y1 - 1999
N2 - The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT. Patients received busulphan at a dose of either 16 mg/kg with cyclophosphamide and ATG (Group A) or 600 mg/m2 (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days. Busulphan levels were analyzed by a modified GC-MS method. The dose of busulphan/kg for patients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUC, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13. There was no significant difference in Vd/F, T1/2 and Kel between the two groups. A significant decrease 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 toxicity due to the higher dose of busulphan was noted. We conclude that busulphan at 600 mg/m2 results in much higher systemic exposure to the drug as compared to 16 mg/kg, without increase in toxicity in children with beta thalassaemia major.
AB - The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT. Patients received busulphan at a dose of either 16 mg/kg with cyclophosphamide and ATG (Group A) or 600 mg/m2 (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days. Busulphan levels were analyzed by a modified GC-MS method. The dose of busulphan/kg for patients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUC, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13. There was no significant difference in Vd/F, T1/2 and Kel between the two groups. A significant decrease 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 toxicity due to the higher dose of busulphan was noted. We conclude that busulphan at 600 mg/m2 results in much higher systemic exposure to the drug as compared to 16 mg/kg, without increase in toxicity in children with beta thalassaemia major.
KW - Bone marrow transplantation
KW - Busulphan
KW - Pharmacokinetics
KW - Thalassaemia
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U2 - 10.1038/sj.bmt.1701814
DO - 10.1038/sj.bmt.1701814
M3 - Article
C2 - 10435727
AN - SCOPUS:0032792198
SN - 0268-3369
VL - 24
SP - 5
EP - 11
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 1
ER -