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

Bone Marrow Transplant. 1999 Jul;24(1):5-11. doi: 10.1038/sj.bmt.1701814.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Bone Marrow Transplantation / methods*
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Busulfan / pharmacokinetics*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Female
  • Hepatic Veno-Occlusive Disease / chemically induced
  • Humans
  • Male
  • Prospective Studies
  • Time Factors
  • Treatment Outcome
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / therapy*

Substances

  • Busulfan