Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology.

ABSTRACT: Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM. In the RAPIRI phase I trial, the combination sirolimus + irinotecan was evaluated as a new treatment for refractory pediatric cancers. Blood sampling at first sirolimus intake (D1) and at steady state (D8), followed by LC/MS² analysis, was used to develop a population pharmacokinetic model (Monolix^® software). A mono-compartmental model with first-order absorption and elimination best fit the data. The o

SUBMITTER: Sabo AN 

PROVIDER: S-EPMC8067051 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature