Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes.

التفاصيل البيبلوغرافية
العنوان:	Pharmacokinetic targeting of i.v. BU with fludarabine as conditioning before hematopoietic cell transplant: the effect of first-dose area under the concentration time curve on transplant-related outcomes.
المؤلفون:	Perkins, J, Field, T, Kim, J, Kharfan-Dabaja, M A, Ayala, E, Perez, L, Fernandez, H, Fancher, K, Tate, C, Shaw, L M, Milone, M C, Gardiner, J A, Miller, S, Anasetti, C
المصدر:	Bone Marrow Transplantation; Nov2011, Vol. 46 Issue 11, p1418-1425, 8p, 3 Charts, 3 Graphs
مصطلحات موضوعية:	FLUDARABINE, HEMATOPOIETIC stem cell transplantation, IMMUNOSUPPRESSION, MORTALITY, RETROSPECTIVE studies, PHARMACOKINETICS
مستخلص:	We used pharmacokinetic (PK) targeting of BU in 145 consecutive patients treated with fludarabine and i.v. BU. BU was given once daily at 130 mg/m² per day on days 1 and 2; doses for days 3 and 4 were adjusted in 92 patients (63%) to an average daily area under the concentration-time curve (AUC) of 5300 μM/min. In the remaining 53 patients, the first-dose AUC was within the target range and no dosing adjustments were required. First-dose AUC, maximum concentration and clearance were not correlated with age, race, ethnicity, performance status, or hematopoietic cell transplant comorbidity index. Women had higher clearance than men (median 2.9 vs 2.5 mL/min/kg; P=0.001). BU toxicities were not associated with first-dose AUC or any other PK parameter measured. First-dose BU AUC was not associated with non-relapse mortality (NRM) or survival, but higher AUC was predictive of relapse. We did not find an increased risk of toxicity or NRM in patients with high first-dose AUC presumably because of the dose adjustment. We conclude that PK targeting of BU as described here provides a simple, safe and effective method of delivering high BU doses before transplantation in a wide variety of patients. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات:	Complementary Index

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