TY - JOUR T1 - I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. AU - Nguyen,L, AU - Fuller,D, AU - Lennon,S, AU - Leger,F, AU - Puozzo,C, PY - 2004/4/6/pubmed PY - 2004/12/16/medline PY - 2004/4/6/entrez SP - 979 EP - 87 JF - Bone marrow transplantation JO - Bone Marrow Transplant VL - 33 IS - 10 N2 - A retrospective population pharmacokinetic (PPK) analysis was performed in 24 pediatric patients (PEDS) (0.45-16.7 years old) receiving i.v. busulfan/cyclophosphamide (i.v. Bu/Cy 4) regimen prior to allogeneic hematopoietic stem cell transplantation. I.V. Bu doses were given as a 2-hour infusion every 6 h over 4 days. Initial dosing of i.v. Bu was 1 mg/kg for children < or =4 years old and 0.8 mg/kg for patients >4 years old. Bu plasma concentrations at doses 1, 9 and 13 were analyzed through a multivariate NONMEM analysis. A close log-linear relationship between body weight (BW) and i.v. Bu clearance was demonstrated with no further age-dependency or gender effect. The interpatient coefficient of variation (CV) in Bu clearance significantly decreased from 56% (covariate-free model) to 19% (BW covariate model) and reproducible i.v. Bu exposure between doses was illustrated (intraindividual CV=9%). Based on the PPK model, a novel Bu dosing regimen (ie: doses in mg/kg adjusted to discrete weight categories) for a better AUC targeting was developed by simulation on 1000 patients. Age-based dosing was demonstrated not to be clinically relevant with i.v. Bu. Use of the new BW-based dosing appears to be more appropriate for the PEDS. SN - 0268-3369 UR - https://www.unboundmedicine.com/medline/citation/15064687/I_V__busulfan_in_pediatrics:_a_novel_dosing_to_improve_safety/efficacy_for_hematopoietic_progenitor_cell_transplantation_recipients_ DB - PRIME DP - Unbound Medicine ER -