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PI‐14
Author(s) -
Hassoun E.,
Shimoni A.,
Nagler A.,
Halkin H.,
Almog S.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.035
Subject(s) - busulfan , pharmacodynamics , medicine , transplantation , stem cell , pharmacokinetics , pharmacology , hematopoietic stem cell transplantation , biology , genetics
BACKGROUND High dose busulfan (BU) is used in preparative chemotherapy regimens for patients undergoing stem cell transplantation (SCT). Myelo‐ and submyeloablative protocols for IV BU, have been developed to achieve stable PK while minimizing toxicity and relapse. We sought to examine the PK of BU in different protocols with vs. without fludarabine and to measure oxidative stress in these protocols. PATIENTS & METHODS 46 SCT patients were studied. Blood samples for PK curves were drawn at the first and mid dosing period. For each protocol PK parameters were estimated using a 1‐compartment open model. RESULTS BU PK parameters, were: t 1/2= 2.83±0.75 hr, Cl=0.17±0.04 (1/hr)/Kg and Vd=0.69±0.19 1/Kg. AUC and Cmax increased lineary with increasing cumulative dose up to 12.8 mg/Kg (r 2 =0.997 and 0.994, respectively). BU PK were not changed by fludarabine. Initial plasma oxidative stress (OS) was high[glutathione oxidative potential (Eh) = (‐285) ± (‐20) mV] compared to normal values[(‐315) ‐ (‐320) mV]. BU aggravated OS: increased Eh by +40 mv and reduced uric acid levels (5.1 ± 2.0 to 2.6 ± 1.1 mg%). CONCLUSIONS IV BU PK are stable, linear, predictable and not affected by fludarabine. The optimization of the therapeutic range of BU AUC and plasma OS for the individual patient requires further research. Clinical Pharmacology & Therapeutics (2005) 79 , P10–P10; doi: 10.1016/j.clpt.2005.12.035