The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients.
Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n=49) yielded the following 95% confidence intervals (CI₉₅): weight-normalized volume of distribution: 0.65-0.73 L/kg; t(1/2): 122-147 min; weight-normalized clearance (CL(n)): 3.4-4.3 mL/min/kg; and area under the curve: 1835-2180 mmol × min/L. From these results, a steady state concentration was calculated with CI₉₅ between 628-746 ng/mL. Comparison between recipients ≤4 vs >4 years old revealed significant differences in t(1/2) (mean: 115 vs 146 min, P=0.008) and CL(n) (mean: 4.4 vs 3.5 mL/min/kg, P=0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing.
Department of Pediatrics, Columbia University, New York, NY, USA.
J B
JB
Le Gall
M C
MC
Milone
I M
IM
Waxman
L M
LM
Shaw
L
L
Harrison
D
D
Duffy
C
C
van de Ven
O
O
Militano
M B
MB
Geyer
E
E
Morris
M
M
Bhatia
P
P
Satwani
D
D
George
J H
JH
Garvin
M B
MB
Bradley
J
J
Schwartz
L A
LA
Baxter-Lowe
M S
MS
Cairo
D000293:Adolescent; D000367:Age Factors; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous
D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; D002066:Busulfan