Journal article

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

Abstract

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) ..

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