Korean J Hematol 2002; 37(2):
Published online June 30, 2002
© The Korean Society of Hematology
동종조혈모세포이식시 전처치제로 투여한 Intravenous Busulfan의 안정성 및 약동학적 특성
박윤희, 이석, 김유진, 이동건, 박치영, 신호진, 김희제, 민창기, 김동욱, 이종욱, 민우성, 김춘추
조선대학교 의과대학 내과학교실,
부산대학교 의과대학 내과학교실,
가톨릭대학교 의과대학 조혈모세포이식센터
Safety and Pharmacokinetics of Intravenous Busulfan as Conditioning prior to Allogeneic Stem Cell Transplantation
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 (0.8㎎/㎏ every 6 hours ×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/㎖ and 951ng/㎖, and the half-life was 2.25h and 3.09h, respectively. The area under the plasma concentration-time curve was 4,596ng·h/㎖ and 3,067ng·h/㎖, 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.
Keywords Intravenous busulfan; Pharmacokinetics; Allogeneic stem cell transplantation;
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Korean J Hematol 2002; 37(2): 127-133
Published online June 30, 2002
Copyright © The Korean Society of Hematology.
동종조혈모세포이식시 전처치제로 투여한 Intravenous Busulfan의 안정성 및 약동학적 특성
박윤희, 이석, 김유진, 이동건, 박치영, 신호진, 김희제, 민창기, 김동욱, 이종욱, 민우성, 김춘추
조선대학교 의과대학 내과학교실,
부산대학교 의과대학 내과학교실,
가톨릭대학교 의과대학 조혈모세포이식센터
Safety and Pharmacokinetics of Intravenous Busulfan as Conditioning prior to Allogeneic Stem Cell Transplantation
Yoon Hee Park, 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
Catholic Hematopoietic Stem Cell Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Korea
Department of Internal Medicine, Chosun University, Kwangju, Korea
Busan National University, Busan, Korea
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 (0.8㎎/㎏ every 6 hours ×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/㎖ and 951ng/㎖, and the half-life was 2.25h and 3.09h, respectively. The area under the plasma concentration-time curve was 4,596ng·h/㎖ and 3,067ng·h/㎖, 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.
Keywords: Intravenous busulfan, Pharmacokinetics, Allogeneic stem cell transplantation,
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