Safety and Pharmacokinetics of Intravenous Busulfan as Conditioning prior to Allogeneic Stem Cell Transplantation.
- Author:
Yoon Hee PARK
1
;
Seok LEE
;
Yoo Jin KIM
;
Dong Gun LEE
;
Chi Young PARK
;
Ho Jin SHIN
;
Hee Je KIM
;
Chang Ki MIN
;
Dong Wook KIM
;
Jong Wook LEE
;
Woo Sung MIN
;
Chun Choo KIM
Author Information
1. Catholic Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Intravenous busulfan;
Pharmacokinetics;
Allogeneic stem cell transplantation
- MeSH:
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*
- From:Korean Journal of Hematology
2002;37(2):127-133
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
