title: Therapeutic drug monitoring for busulfan in plasma during conditioning chemotherapy for autologous stem cell transplantation in relapsed primary cerebral lymphoma.
abstract: Therapeutic drug monitoring for busulfan in plasma during conditioning chemotherapy for autologous stem cell transplantation in relapsed primary cerebral lymphoma has not previously been reported. This case involved a 49-year-old man with relapsed primary cerebral lymphoma who received busulfan (8 mg/kg total dose; 2.67 mg/kg as a 3-hour IV infusion each of days -6 through -4) as part of a multiagent chemotherapy conditioning regimen. Multiple plasma samples were collected for all 3 doses and busulfan was quantified by liquid chromatography tandem mass spectrometry. A 1-compartment model was individually fitted to the concentration-time data for each dose. Clearance decreased across the 3 days of treatment (4.84, 4.06, and 3.04 mL/min/kg, respectively), whereas at the same times half-life increased (2.64, 3.18, and 4.17 hours, respectively), as did area under the plasma concentration-time curve0-infinity (9170, 10,900, and 14,600 microg h/L, respectively). Volume of distribution was similar across this time (1-1.1 L/kg). Indices of both renal and hepatic function did not indicate any significant diminution in likely clearance capacity for busulfan. There was also no compelling evidence for drug interactions that could decrease clearance. We conclude that therapeutic drug monitoring should be recommended for future cases of this rare disease, with a view to developing a target-concentration intervention strategy and improving outcomes.
authors.affiliation: Haematology Department, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cull
authors.forename: Sean
authors.initials: S
authors.lastname: O'Halloran
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Ilett
mesh_terms: D001521:Behavior Therapy / Q000639:trends; D002066:Busulfan / Q000097:blood* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D006207:Half-Life; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008111:Liver Function Tests; D055502:Secondary Prevention; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous / Q000639:trends
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan