Back to Search
Start Over
Population Pharmacokinetics and Safety of Dasatinib in Chinese Children with Core-Binding Factor Acute Myeloid Leukemia
- Source :
- Clinical Pharmacokinetics. 61:71-81
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Dasatinib, an orally administered Src-family kinase inhibitor, is combined with the standard chemotherapeutic regimen to enhance antineoplastic activity against core-binding factor acute myeloid leukemia (CBF-AML) in adults; however, limited data are available for use in children. In the present study, we studied the pharmacokinetics and safety of dasatinib in children. Dasatinib (60 or 80 mg/m2 once daily) was administered to 20 children with CBF-AML. Blood samples were collected and drug concentrations were quantified by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). Population pharmacokinetic analysis and Monte-Carlo simulations were performed using NONMEM software, and safety analyses were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 (NCT03844360). Twenty pediatric patients (3.3–14.4 years of age) were included, and a total of 40 dasatinib concentrations were available for population pharmacokinetic analysis. The mean (standard deviation) of the estimated area under the concentration-time curve extrapolated to steady state (AUCss) of dasatinib 60 and 80 mg/m2 was 366.1 (146.6) ng·h/mL and 425.3 (150.7) ng·h/mL, respectively. The majority of adverse events were grade 1/2 in severity, including thrombocytopenia, rash, and pain in the extremities. The estimated cumulative incidence of complete remission and complete molecular response were 95.0% and 75.5%, respectively. The population pharmacokinetics of orally administered dasatinib were evaluated in pediatric CBF-AML patients. The AUCss of dasatinib (80 mg/m2) in CBF-AML pediatric patients was similar to those of dasatinib (100 mg) in adult patients. Dasatinib is well-tolerated in pediatric patients with CBF-AML.
- Subjects :
- Pharmacology
medicine.medical_specialty
education.field_of_study
business.industry
Population
Common Terminology Criteria for Adverse Events
Gastroenterology
NONMEM
Dasatinib
Regimen
Pharmacokinetics
hemic and lymphatic diseases
Internal medicine
Medicine
Pharmacology (medical)
Cumulative incidence
business
Adverse effect
education
medicine.drug
Subjects
Details
- ISSN :
- 11791926 and 03125963
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Clinical Pharmacokinetics
- Accession number :
- edsair.doi...........e52c4cd7b64c8c53ba23a68ded527e01