The pharmacokinetics and safety of twice daily i.v. BU during conditioning in pediatric allo-SCT recipients
Autor: | J B Le Gall, Deirdre Duffy, O. Militano, Joseph E. Schwartz, Erin Morris, Leslie M. Shaw, C. van de Ven, Diane George, Prakash Satwani, James Garvin, I M Waxman, Michael C. Milone, L.A. Baxter-Lowe, Monica Bhatia, Lauren Harrison, M B Bradley, Mark B. Geyer, Mitchell S. Cairo |
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Rok vydání: | 2012 |
Předmět: |
Male
Transplantation Conditioning Adolescent Metabolic Clearance Rate Drug Administration Schedule Cohort Studies Pharmacokinetics immune system diseases hemic and lymphatic diseases Medicine Humans Transplantation Homologous Child Infusions Intravenous Antineoplastic Agents Alkylating Busulfan Transplantation business.industry Graft Survival Age Factors Infant Hematology Allo sct Myeloablative Agonists surgical procedures operative Anesthesia Child Preschool Conditioning Drug Therapy Combination Female business therapeutics human activities Follow-Up Studies Half-Life Stem Cell Transplantation |
Zdroj: | Bone marrow transplantation. 48(1) |
ISSN: | 1476-5365 |
Popis: | Intravenous BU divided four times daily (q6 h) has been shown to be safe and effective in pediatric allo-SCT recipients. Though less frequent dosing is desirable, pharmacokinetic (PK) data on twice daily (q12 h) i.v. BU administration in pediatric allo-SCT recipients is limited. We prospectively examined the PK results in a cohort of pediatric allo-SCT recipients receiving i.v. BU q12 h as part of conditioning before allo-SCT. BU levels were obtained after the first dose of conditioning. PK parameter analysis (n=49) yielded the following 95% confidence intervals (CI₉₅): weight-normalized volume of distribution: 0.65-0.73 L/kg; t(1/2): 122-147 min; weight-normalized clearance (CL(n)): 3.4-4.3 mL/min/kg; and area under the curve: 1835-2180 mmol × min/L. From these results, a steady state concentration was calculated with CI₉₅ between 628-746 ng/mL. Comparison between recipients ≤4 vs4 years old revealed significant differences in t(1/2) (mean: 115 vs 146 min, P=0.008) and CL(n) (mean: 4.4 vs 3.5 mL/min/kg, P=0.038). Intravenous BU q12 h had a comparable PK to i.v. BU q6 h PK seen in the literature, and in pediatric allo-SCT recipients, is a feasible, attractive alternative to i.v. q6h dosing. |
Databáze: | OpenAIRE |
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