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

被引:117
作者
McCune, JS
Gibbs, JP
Slattery, JT
机构
[1] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
[2] Univ Washington, Dept Pharm, Seattle, WA 98195 USA
[3] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA
关键词
D O I
10.2165/00003088-200039020-00005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
High dosage busulfan (1 mg/kg orally every 6 hours x 16 doses) is frequently used in preparative regimens for haemopoietic stem cell transplantation (HSCT). Busulfan is well absorbed after oral administration, exhibits low protein binding and is metabolised through conjugation with glutathione to form a thiophenium ion. At a given dose, there is considerable variability in the systemic exposure of busulfan, typically expressed as area under the plasma concentration-time curve (AUC) or average concentration at steady state (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 and a higher conjugation rate of busulfan with glutathione in the enterocyte. Several investigators have identified relationships between busulfan C-SS and outcome in patients undergoing HSCT. Busulfan concentration-response relationships are regimen-, age- and disease-dependent. The busulfan/cyclophosphamide (BU/CY) regimen is the only regimen for which substantial concentration-outcome data exist. Generally, the risk of hepatic veno-occlusive disease 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 relapse in chronic myelogenous leukaemia occur in patients with a busulfan C-SS > 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.
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页码:155 / 165
页数:11
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