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Conditioning Regimens

F-ara-A pharmacokinetics during reduced-intensity conditioning therapy with fludarabine and busulfan

Bone Marrow Transplantation volume 39, pages 201–206 (2007)Cite this article

Abstract

Fludarabine is commonly used in combination with busulfan as part of conditioning regimens before allogeneic stem cell transplantation. So far, no data are available on busulfan–fludarabine drug interactions in transplant recipients. The pharmacokinetic (PK) properties of F-ara-A (9-β-D-arabinosyl-2-fluoradenine) before and after application of busulfan were prospectively investigated in 16 patients with hematological malignancies. The conditioning regimen consisted of intravenous fludarabine 30 mg/m2 over 30 min from day −6 to day −3, and oral busulfan given at 1 mg/kg every 6 h from day −5 to day −2. PK parameters of F-ara-A, derived from plasma and urine on day −6, −5, −4 and −3, were determined using high-performance liquid chromatography (HPLC). AUC, Cmax, t1/2, Cltotal and VSS were 21.9 μ Mh, 3.5 μ M, 13.0 h, 4.3 l/h/m2, 60.0 l/m2 on day −6 and 22.4 μ Mh, 3.5 μ M, 14.0 h, 4.7 l/h/m2, 69.0 l/m2 on day −5 to (−2), respectively. Clrenal and the urine-recovery were 4.8 l/h, 43.7% of the fludarabine dose on day −6 and 3.9 l/h, 44.2% of the fludarabine dose on day −5 to (−2), respectively. There were no changes in PK parameters of fludarabine given before and after intake of busulfan. This implies that a clinically relevant busulfan–fludarabine drug interaction is unlikely.

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Authors and Affiliations

  1. Department of Haematology/Oncology, University Hospital Dresden, Dresden, Germany

    M Bonin, S Pursche, T Bergeman, T Leopold, T Illmer, G Ehninger & M Bornhauser

  2. Department of Internal Medicine II, Carl-von-Basedow Klinikum, Merseburg, Germany

    E Schleyer

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  1. M Bonin
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  2. S Pursche
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Correspondence to M Bornhauser.

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Bonin, M., Pursche, S., Bergeman, T. et al. F-ara-A pharmacokinetics during reduced-intensity conditioning therapy with fludarabine and busulfan. Bone Marrow Transplant 39, 201–206 (2007). https://doi.org/10.1038/sj.bmt.1705565

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