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

B. Poonkuzhali, A. Srivastava, M. H. Quernin, D. Dennison, E. J. Aigrain, A. S. Kanagasabapathy, R. Krishnamoorthy, M. Chandy

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Abstract

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.

Original languageEnglish
Pages (from-to)5-11
Number of pages7
JournalBone Marrow Transplantation
Volume24
Issue number1
Publication statusPublished - 1999

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Keywords

  • Bone marrow transplantation
  • Busulphan
  • Pharmacokinetics
  • Thalassaemia

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Poonkuzhali, B., Srivastava, A., Quernin, M. H., Dennison, D., Aigrain, E. J., Kanagasabapathy, A. S., ... Chandy, M. (1999). Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation. Bone Marrow Transplantation, 24(1), 5-11.