Plasma concentration monitoring of busulfan - Does it improve clinical outcome?

Citation
Js. Mccune et al., Plasma concentration monitoring of busulfan - Does it improve clinical outcome?, CLIN PHARMA, 39(2), 2000, pp. 155-165
Citations number
54
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOKINETICS
ISSN journal
03125963 → ACNP
Volume
39
Issue
2
Year of publication
2000
Pages
155 - 165
Database
ISI
SICI code
0312-5963(200008)39:2<155:PCMOB->2.0.ZU;2-X
Abstract
High dosage busulfan (1 mg/kg orally every 6 hours x 16 doses) is frequentl y used in preparative regimens for haemopoietic stem cell transplantation ( HSCT). Busulfan is well absorbed after oral administration, exhibits low pr otein binding and is metabolised through conjugation with glutathione to fo rm a thiophenium ion. At a given dose, there is considerable variability in the systemic exposure of busulfan, typically expressed as area under the p lasma concentration-time curve (AUC) or average concentration at steady sta te (C-SS) Relative to that in adolescents and adults, patients less than 4 years of age have an increased apparent oral clearance (CL/F) of busulfan a nd a higher conjugation rate of busulfan with glutathione in the enterocyte . Several investigators have identified relationships between busulfan C-SS a nd outcome in patients undergoing HSCT. Busulfan concentration-response rel ationships are regimen-, age- and disease-dependent. The busulfan/cyclophos phamide (BU/CY) regimen is the only regimen for which substantial concentra tion-outcome data exist. Generally, the risk of hepatic veno-occlusive dise ase is increased with busulfan C-SS > 900 mu g/L The impact of busulfan C-SS on veno-occlusive disease may be influenced by the age of the patient and the dose of cyclophosphamide. Lower rates of rel apse in chronic myelogenous leukaemia occur in patients with a busulfan C-S S > 917 mu g/L without an increased risk of toxicity. Busulfan C-SS is also related to the engraftment rate in children, and escalating busulfan doses to achieve a target C-SS > 600 mu g/L improves graft retention. Therapeutic drug monitoring of busulfan should be performed to maximise the likelihood of engraftment and minimise the risk of toxicity and relapse in HSCT patients receiving the BU/CY preparative regimen.