title: Busulfan pharmacokinetics in bone marrow transplant patients: is drug monitoring warranted?
abstract: Pharmacokinetics were studied in relation to hepatic side-effects in 20 patients (19 adults aged 18-53 years and one child of 11 years) undergoing BMT after conditioning with 1 mg/kg busulfan (every 6 hours for 16 doses). Busulfan was quantitated in plasma samples at 10 time points within the 6 h dosing interval using HPLC before and after dose numbers 1, 2, 5, 13 and 14. For 13 patients data on all five doses are available; for the remaining seven patients three to four doses were studied. Mean maximum concentrations were 1512 ng/ml; mean trough levels for second and subsequent doses were 615 ng/ml. Maxima (Cmax) tended to be lower and times of maxima (Tmax) were later when busulfan was taken with a meal. Correlation of the area under the concentration versus time curve (AUC0-6h) between different doses was low within patients. In several patients problems with compartmental fitting of concentration data were observed mainly caused by the short dosing interval, which made estimates of T1/2 and model derived AUCs unstable. Three patients experienced hepatic veno-occlusive disease; kinetic parameters were not helpful in describing a particulate risk constellation for this subgroup. In our experience, the role of drug monitoring in this setting needs to be defined more clearly.
authors.affiliation: Department of Haematology and Oncology, University of Tübingen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schuler
authors.forename: S
authors.initials: S
authors.lastname: Schroer
authors.forename: A
authors.initials: A
authors.lastname: Kühnle
authors.forename: J
authors.initials: J
authors.lastname: Blanz
authors.forename: K
authors.initials: K
authors.lastname: Mewes
authors.forename: I
authors.initials: I
authors.lastname: Kumbier
authors.forename: B
authors.initials: B
authors.lastname: Proksch
authors.forename: K P
authors.initials: KP
authors.lastname: Zeller
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000502:physiology*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D016903:Drug Monitoring / Q000379:methods; D004435:Eating; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D012307:Risk Factors
chemical_list: D002066:Busulfan; D008787:Metoclopramide