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I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients.
Bone Marrow Transplant. 2004 May; 33(10):979-87.BM

Abstract

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.

Authors+Show Affiliations

Clinical Pharmacokinetic Department, Institut de Recherche Pierre Fabre, 11 rue Théron Périé, 81106 Castres Cedex, France. laurent.nguyen@pierre-fabre.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article

Language

eng

PubMed ID

15064687

Citation

Nguyen, L, et al. "I.V. Busulfan in Pediatrics: a Novel Dosing to Improve Safety/efficacy for Hematopoietic Progenitor Cell Transplantation Recipients." Bone Marrow Transplantation, vol. 33, no. 10, 2004, pp. 979-87.
Nguyen L, Fuller D, Lennon S, et al. I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. Bone Marrow Transplant. 2004;33(10):979-87.
Nguyen, L., Fuller, D., Lennon, S., Leger, F., & Puozzo, C. (2004). I.V. busulfan in pediatrics: a novel dosing to improve safety/efficacy for hematopoietic progenitor cell transplantation recipients. Bone Marrow Transplantation, 33(10), 979-87.
Nguyen L, et al. I.V. Busulfan in Pediatrics: a Novel Dosing to Improve Safety/efficacy for Hematopoietic Progenitor Cell Transplantation Recipients. Bone Marrow Transplant. 2004;33(10):979-87. PubMed PMID: 15064687.
* Article titles in AMA citation format should be in sentence-case
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_ L2 - https://doi.org/10.1038/sj.bmt.1704446 DB - PRIME DP - Unbound Medicine ER -