Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites
Zheng Liu, Jennifer H Martin, Winston Liauw, Sue-Anne Mclachlan, Emma Link, Anetta Matera, Michael Thompson, Michael Jefford, Rod J Hicks, Carleen Cullinane, Athena Hatzimihalis, Ian Campbell, Simone Crowley, Phillip J Beale, Christos S Karapetis, Timothy Price, Mathew E Burge, Michael Michael
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY | SPRINGER HEIDELBERG | Published : 2021
BACKGROUND: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. METHODS: Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) ..View full abstract
Related Projects (1)
Awarded by Australian National Health and Medical Research Council
Funding support by the (1) Australian National Health and Medical Research Council (Grant No. 628564) and (2) the Pathways to Cancer Freedom Grant, Cancer Council NSW 2018, Australia.