The application of virtual therapeutic drug monitoring to assess the pharmacokinetics of imatinib in a Chinese Cancer population group

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Abstract

PURPOSE: Imatinib is used in gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia (CML). Oncology patients demonstrate altered physiology compared to healthy adults, e.g. reduced haematocrit, increased α-1 acid glycoprotein, decreased albumin and reduced glomerular filtration rate (GFR), which may influence imatinib pharmacokinetics. Given that Chinese cancer patients often report raised imatinib plasma concentrations and wider inter-individual variability reported in trough concentration when compared to Caucasian cancer patients, therapeutic drug monitoring (TDM) has been advocated.

METHOD: This study utilised a previously validated a Chinese cancer population and assessed the impact of imatinib virtual-TDM in Chinese and Caucasian cancer populations across a dosing range from 200-800 mg daily.

RESULTS: Staged dose titration to 800 mg daily, resulted in recapitulation to within the target therapeutic range for 50 % (Chinese) and 42.1% (Caucasian) subjects possessing plasma concentration < 550 ng/mL when dosed at 400 mg daily. For subjects with plasma concentrations >1500 ng/mL when dosed at 400 mg daily, a dose reduction to 200 mg once daily was able to recover 67 % (Chinese) and 87.4 % (Caucasian) patients to the target therapeutic range.

CONCLUSION: Virtual TDM highlights the benefit of pharmacokinetic modelling to optimising treatments in challenging oncology population groups.

Original languageEnglish
Pages (from-to)599-609
JournalJournal of Pharmaceutical Sciences
Volume112
Issue number2
Early online date3 Oct 2022
DOIs
Publication statusPublished - Feb 2023

Bibliographical note

Copyright © 2022, The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)

Keywords

  • Cancer
  • Chinese
  • Imatinib
  • Pharmacokinetics
  • Therapeutic drug monitoring

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