Pharmacokinetics of busulfan in pediatric and adult patients prior to hematopoietic stem cell transplantation
- Author:
Ping ZHENG
1
Author Information
- Publication Type:Journal Article
- Keywords: Adults; Busulfan; Children; Hematopoietic stem cell transplantation; Pharmacokinetics; Preparative regimen
- From: Chinese Pharmaceutical Journal 2013;48(13):1088-1093
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To study the pharmacokinetic profiles of intravenous busulfan in Chinese pediatric and adult patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT). METHODS: Blood samples of 22 pediatric and 9 adult patients were collected following the last dose of a 3-4 d, 12-16 doses intravenous busulfan regimen in children with thalassemia and adult leukemia patients or of a 4 d, once-daily intravenous busulfan regimen in pediatric hematologic malignancies patients. The plasma concentrations of busulfan were determined by LC/MS/MS, and the pharmacokinetic parameters of busulfan were calculated by DAS. RESULTS: The plasma concentration-time curves after the last dose intravenous busulfan in 31 patients were fitted to a two-compartment model. The main pharmacokinetic parameters in pediatric and adult patients undergoing allo-HSCT were as follow: CL(0.4±0.2) and(0.2±0.1) L·h-1·kg-1, t1/2β(3.3±1.5) and(3.1±0.8) h, Vd(0.6±0.8) and(0.4±0.2) L·kg-1, and Cav(590.4±265.3) and(572.2±214.7) μg·L-1, respectively. The CL after intravenous administration of busulfan was different between pediatric and adult patients(P<0.05). The t1/2β, Vd, CL, K10, and K12 were significantly different(P<0.01) between the pediatric patients with thalassemia and hematologic malignancies. CONCLUSION: The inter- and intra-patient variabilities in the main pharmacokinetic parameters of intravenous busulfan in children and adults are statistically significant. The difference of pharmacokinetic parameters between children with different diseases is obvious. The t1/2β and Vd in pediatric patients with thalassemia have significant reduction. More research is warranted on intravenous busulfan pharmacokinetics in Chinese patients, and therapeutic drug monitoring and appropriate dose adjustment are recommended.
