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.
Bibliographical noteCopyright © 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/)
- Therapeutic drug monitoring