Busulphan in blood and marrow transplantation: dose, route, frequency and role of therapeutic drug monitoring.
Busulphan (Bu) is an alkylating agent that, when combined with agents such as cyclophosphamide (Cy), ablates the bone marrow prior to blood or marrow transplantation. There is wide inter- and intra- patient variability in Bu pharmacokinetics. Early pharmacodynamic studies suggested a significant relationship between high Bu exposure and the occurrence of veno-occlusive disease of the liver, but were not performed in uniform patient populations and tended to use a Cy dose of 200 mg/kg. Pharmacodynamic studies in uniform patient populations, with lower doses of Cy, contradict these results. Despite 20 years of clinical use, pharmacodynamic studies are still required to define the relationship between Bu exposure and optimal transplant outcome, and these may vary according to age, disease, transplant type and conditioning regimen. Given the availability now of an intravenous formulation, it is timely to review how and why we are giving Bu. Administration of single daily doses of Bu has been shown to be safe and effective with oral Bu and has been used with i.v. preparations. This simple administration provides accuracy in measuring exposure, which is ideal for pharmacokinetic studies, and provides the possibility of defining a target exposure level associated with a good outcome. Only when this target is defined will therapeutic drug monitoring be useful to minimise toxicity, maximise efficacy and improve transplant outcome.
Nath
Christa Ellen
CE
Department of Biochemistry, The Children's Hospital at Westmead, Hawkesbury Rd, Westmead, Sydney, NSW, 2145, Locked Bag 4001, Westmead, Sydney, NSW, 2145, Australia. christan@chw.edu.au
Shaw
Peter John
PJ
D000284:Administration, Oral; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D006801:Humans; D007262:Infusions, Intravenous
D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan