title: Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation.
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.
authors.affiliation: Department of Hematology, Christian Medical College and Hospital, Vellore, Nadu, India.
authors.forename: B
authors.initials: B
authors.lastname: Poonkuzhali
authors.forename: A
authors.initials: A
authors.lastname: Srivastava
authors.forename: M H
authors.initials: MH
authors.lastname: Quernin
authors.forename: D
authors.initials: D
authors.lastname: Dennison
authors.forename: E J
authors.initials: EJ
authors.lastname: Aigrain
authors.forename: A S
authors.initials: AS
authors.lastname: Kanagasabapathy
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: M
authors.initials: M
authors.lastname: Chandy
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000628:therapy*
chemical_list: D002066:Busulfan