کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5524419 1546242 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Clinical Research: PediatricPretransplant Absolute Lymphocyte Counts Impact the Pharmacokinetics of Alemtuzumab
ترجمه فارسی عنوان
تحقیقات بالینی: شمارش لنفوسیتهای مطلق پروتئین تلقی می شود تا فارماکوکینتیک های آلومتوسومب
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی


- The PK of subcutaneous alemtuzumab given to pediatric allogeneic HCT patients is presented.
- Almost all patients have persistence of lytic levels of alemtuzumab beyond day 0.
- Most patients have levels of alemtuzumab in excess of that needed to reduce the risk of acute GVHD.
- The PK of alemtuzumab is significantly affected by pretransplant ALC.

Alemtuzumab is frequently used as part of reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (HCT) in pediatric patients with nonmalignant diseases. We previously suggested an optimal day 0 targeted range of alemtuzumab, but there are no pediatric data regarding the pharmacokinetics (PK) of subcutaneous alemtuzumab to guide precision dosing trials. The goal of this study was to prospectively characterize alemtuzumab PK and to explore absolute lymphocyte count (ALC) as a predictor of interindividual variability. We prospectively enrolled 23 patients who received an alemtuzumab, fludarabine, and melphalan RIC regimen. Seventeen patients completed study and received 1 mg/kg alemtuzumab divided over 5 days subcutaneously, starting on day −14. The median age was 7 years (range, .5 to 18). Blood sampling for PK measurements and descriptive PK analyses were performed. The median maximum alemtuzumab concentration was 2.39 µg/mL (interquartile range, 1.98 to 2.92). The median terminal half-life was 5.2 days (interquartile range, 2.7 to 7.8). The median concentration at day 0 was 1.27 µg/mL (interquartile range, .35 to 1.51). Importantly, day 0 alemtuzumab levels and area under the curve negatively correlated with predose ALC and ALC area-time, respectively. In conclusion, we reported the PK of subcutaneous alemtuzumab given to pediatric allogeneic HCT patients and observed that almost all patients have persistence of lytic levels of alemtuzumab beyond day 0, at levels in excess of that needed to reduce the risk of acute graft-versus-host disease. Additionally, levels correlate with pretransplant ALC. These results will allow the development of population PK models for precision dosing trials.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biology of Blood and Marrow Transplantation - Volume 23, Issue 4, April 2017, Pages 635-641
نویسندگان
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