Tags

Type your tag names separated by a space and hit enter

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.
Cancer Chemother Pharmacol. 2008 Jan; 61(1):113-23.CC

Abstract

INTRODUCTION

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability.

PURPOSE

A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated.

METHOD

Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years).

RESULTS

No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

Authors+Show Affiliations

Institut Gustave Roussy, Villejuif, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

17393167

Citation

Vassal, G, et al. "Prospective Validation of a Novel IV Busulfan Fixed Dosing for Paediatric Patients to Improve Therapeutic AUC Targeting Without Drug Monitoring." Cancer Chemotherapy and Pharmacology, vol. 61, no. 1, 2008, pp. 113-23.
Vassal G, Michel G, Espérou H, et al. Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemother Pharmacol. 2008;61(1):113-23.
Vassal, G., Michel, G., Espérou, H., Gentet, J. C., Valteau-Couanet, D., Doz, F., Mechinaud, F., Galambrun, C., Neven, B., Zouabi, H., Nguyen, L., & Puozzo, C. (2008). Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. Cancer Chemotherapy and Pharmacology, 61(1), 113-23.
Vassal G, et al. Prospective Validation of a Novel IV Busulfan Fixed Dosing for Paediatric Patients to Improve Therapeutic AUC Targeting Without Drug Monitoring. Cancer Chemother Pharmacol. 2008;61(1):113-23. PubMed PMID: 17393167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring. AU - Vassal,G, AU - Michel,G, AU - Espérou,H, AU - Gentet,J C, AU - Valteau-Couanet,D, AU - Doz,F, AU - Mechinaud,F, AU - Galambrun,C, AU - Neven,B, AU - Zouabi,H, AU - Nguyen,L, AU - Puozzo,C, Y1 - 2007/03/29/ PY - 2006/12/21/received PY - 2007/03/02/accepted PY - 2007/3/30/pubmed PY - 2007/12/21/medline PY - 2007/3/30/entrez SP - 113 EP - 23 JF - Cancer chemotherapy and pharmacology JO - Cancer Chemother Pharmacol VL - 61 IS - 1 N2 - INTRODUCTION: Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. PURPOSE: A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. METHOD: Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). RESULTS: No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window. SN - 0344-5704 UR - https://www.unboundmedicine.com/medline/citation/17393167/Prospective_validation_of_a_novel_IV_busulfan_fixed_dosing_for_paediatric_patients_to_improve_therapeutic_AUC_targeting_without_drug_monitoring_ L2 - https://dx.doi.org/10.1007/s00280-007-0455-2 DB - PRIME DP - Unbound Medicine ER -