OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.
Adult* ; Area Under Curve ; Behavior Therapy ; Body Weight ; Busulfan* ; Drug Dosage Calculations ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Pharmacokinetics ; Prospective Studies*

BACKGROUND: The unpredictable intestinal absorption and bioavailability of oral busulfan (BU) has limited the drug's use in high-dose pretransplant conditioning therapy. To overcome these problems, several trials for the evaluation of pharmacokinetics and clinical usefulness of an intravenous BU (IVBU) formulation have been reported. Here we present clinical and pharmacokinetic data on patients receiving IVBU as a component of conditioning regimens for allogeneic stem cell transplantation (SCT) in our center. METHODS: A total of 6 adult patients were entered onto this study. All patients were treated with IVBU (0.8mg/kg every 6 hours x 8~16)-containing conditioning regimen followed by HLA-identical allogeneic SCT. We also investigated the pharmacokinetics of IVBU using high-performance liquid chromatography in two cases. RESULTS: All patients achieved successful engraftment. No patient experienced hepatic veno-occlusive disease or neurologic toxicity. Five of 6 patients still alive in complete remission have been followed for 8~12 months after SCT. The measured maximum concentration for the first dose was 1,175ng/mL and 951ng/mL, and the half-life was 2.25h and 3.09h, respectively. The area under the plasma concentration-time curve was 4,596ng h/ mL and 3,067ng h/mL, respectively. There was no significant difference between the first and last dose pharmacokinetic parameters. CONCLUSION: We suggest that IVBU should be considered as appropriate replacement for oral BU in pretransplant conditioning therapy prior to SCT in Korea. Further studies with sizable patients are needed to define the role of IVBU in SCT setting.
Adult ; Behavior Therapy ; Biological Availability ; Busulfan* ; Chromatography, Liquid ; Half-Life ; Hepatic Veno-Occlusive Disease ; Humans ; Intestinal Absorption ; Korea ; Pharmacokinetics* ; Plasma ; Stem Cell Transplantation* ; Stem Cells*