title: Population pharmacokinetic-based dosing of intravenous busulfan in pediatric patients.
abstract: 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.
authors.affiliation: 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.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Booth
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.forename: Ramzi
authors.initials: R
authors.lastname: Dagher
authors.forename: Donna
authors.initials: D
authors.lastname: Griebel
authors.forename: Shari
authors.initials: S
authors.lastname: Lennon
authors.forename: David
authors.initials: D
authors.lastname: Fuller
authors.forename: Chandra
authors.initials: C
authors.lastname: Sahajwalla
authors.forename: Mehul
authors.initials: M
authors.lastname: Mehta
authors.forename: Jogarao V S
authors.initials: JV
authors.lastname: Gobburu
mesh_terms: 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
chemical_list: D000477:Alkylating Agents; D002066:Busulfan