title: F-ara-A pharmacokinetics during reduced-intensity conditioning therapy with fludarabine and busulfan.
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-beta-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/m(2) 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, C(max), t(1/2), Cl(total) and V(SS) were 21.9 microMh, 3.5 microM, 13.0 h, 4.3 l/h/m(2), 60.0 l/m(2) on day -6 and 22.4 microMh, 3.5 microM, 14.0 h, 4.7 l/h/m(2), 69.0 l/m(2) on day -5 to (-2), respectively. Cl(renal) 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.
authors.affiliation: Department of Haematology/Oncology, University Hospital Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bonin
authors.forename: S
authors.initials: S
authors.lastname: Pursche
authors.forename: T
authors.initials: T
authors.lastname: Bergeman
authors.forename: T
authors.initials: T
authors.lastname: Leopold
authors.forename: T
authors.initials: T
authors.lastname: Illmer
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.forename: E
authors.initials: E
authors.lastname: Schleyer
authors.forename: M
authors.initials: M
authors.lastname: Bornhauser
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine