Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer.

ABSTRACT:

Purpose

4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination.

Methods

We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 singl

SUBMITTER: Navarro SL 

PROVIDER: S-EPMC11438565 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature