The importance of therapeutic drug monitoring (TDM) for parenteral busulfan dosing in conditioning regimen for hematopoietic stem cell transplantation (HSCT) in children
Language English Country United States Media electronic
Document type Journal Article
PubMed
24811685
DOI
10.12659/aot.889933
PII: 889933
Knihovny.cz E-resources
- MeSH
- Adjuvants, Immunologic administration & dosage MeSH
- Busulfan administration & dosage adverse effects pharmacokinetics MeSH
- Child MeSH
- Ditiocarb administration & dosage MeSH
- Infusions, Intravenous MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Drug Monitoring methods MeSH
- Myeloablative Agonists administration & dosage adverse effects pharmacokinetics MeSH
- Child, Preschool MeSH
- Transplantation Conditioning adverse effects methods MeSH
- Body Weight MeSH
- Hematopoietic Stem Cell Transplantation methods MeSH
- Chromatography, High Pressure Liquid MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adjuvants, Immunologic MeSH
- Busulfan MeSH
- Ditiocarb MeSH
- Myeloablative Agonists MeSH
BACKGROUND: Series of observations indicate PK/PD variability challenging the accuracy of the body-weight based busulfan (Bu) dosing schedule for (HSCT) conditioning therapy. The purpose of this communication is to describe the frequency of dose changes in initially body-weight-based fixed IV Bu dose and to emphasize the importance of TDM. MATERIAL AND METHODS: Sixty-two children (ages 2 months-18 years) were treated with IV busulfan doses based on body weight for myeloablation. TDM utilizing a limited sample strategy (trough concentration immediately before the 5th dose, followed by samples immediately after the end of the 2-h infusion peak, 4 h, and 6 h from initiation of the infusion) was performed in 46 of 62 subjects. Busulfan concentrations were determined by high-performance liquid chromatography (HPLC). AUC was calculated according to the trapezoidal rule. RESULTS: We observed trough levels of 25-1244 µg/L, peak levels of 849-4586 µg/L, and AUC of 2225-12818 µg/L·h following body weight-based high-dose busulfan. The doses were changed in 54% of cases. AUC in 5 of 9 patients with VOD were within target, in 3 patients AUS was higher, and in 1 patient AUC was lower. One of the 2 patients with neurotoxicity had higher AUC. Engraftment was 100%, but relapse occurred in 25% of cases. CONCLUSIONS: Our results demonstrate that even with IV busulfan, intra-individual PK/PD variability is challenging. Although AUC does not necessarily correspond with outcomes (due to the role of other factors the fact that doses were changed in 54% of cases underlines the importance of TDM.
References provided by Crossref.org
Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation
