Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients.
The objective of this study was to characterize the pharmacokinetics (PK) of intravenous busulfan in pediatric patients and provide dosing recommendations. Twenty-four pediatric patients were treated with intravenous busulfan, 1.0 or 0.8 mg/kg for ages < or = 4 years or > 4 years, respectively, 4 times a day for 4 days. Dense PK sampling was performed. Body weight, age, gender, and body surface area were explored for effects on PK, and Monte Carlo simulations were performed to assess different dosing regimens. The PK of intravenous busulfan was described by a 1-compartment model with clearance of 4.04 L/h/20 kg and volume of distribution of 12.8 L/20 kg. Simulations indicated that the mg/kg and mg/m2 regimens were similar and achieved the desired target exposure in approximately 60% of patients. This model suggests that patients < or = 12 kg should be dosed at 1.1 mg/kg and those > 12 kg dosed at 0.8 mg/kg. Therapeutic drug monitoring and dose adjustment will further improve therapeutic targeting.
Booth
Brian P
BP
Food and Drug Administration, Office of Clinical Pharmacology, Division of Clinical Pharmacology 5, 10903 New Hampshire Avenue, Building 21, Room 3668, Silver Spring, MD 20993-0002, USA.
Rahman
Atiqur
A
Dagher
Ramzi
R
Griebel
Donna
D
Lennon
Shari
S
Fuller
David
D
Sahajwalla
Chandra
C
Mehta
Mehul
M
Gobburu
Jogarao V S
JV
D000367:Age Factors; D000477:Alkylating Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001830:Body Surface Area; D001835:Body Weight; D002066:Busulfan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy; D012737:Sex Factors
D000477:Alkylating Agents; D002066:Busulfan