Abstract:
Objective
To ascertain the impact of CYP3A4 polymorphism on the therapeutic
outcome of imatinib and its trough concentration
Study design
Descriptive analytical study
Place and duration of the study
This study was conducted in the Department of Pharmacology &
Therapeutics, Islamic International Medical College, between
December 2020 and February 2022, in collaboration with the Institute
of Biomedical Genetic Engineering, KRL Hospital Islamabad.
Methods
Patients with Chronic Myeloid Leukaemia age range–18-70 years were
included in this study. One group comprised responders and the
other group comprised non-responders. Imatinib trough levels in
both groups were determined using High-performance Liquid
Chromatography and compared, and the association was determined
with therapeutic outcomes. DNA was extracted, and the PCR
Open Peer Review
Approval Status
1 2
version 1
22 Apr 2024 view view
Aijun Zhang , Shandong University,
Shandong, China
1.
Nicholas Cross, University of Southampton,
Southampton, UK
2.
Any reports and responses or comments on the
article can be found at the end of the article.
Page 1 of 11
F1000Research 2024, 13:310 Last updated: 22 AUG 2024
Associated Research Article
Gazali M, Effendi I, Husni A et al. » Sargassum sp. extract improve hematological profile of tilapia fish (Oreochromis niloticus),
F1000Research 2024, 12:293 (https://doi.org/10.12688/f1000research.128819.4)
Corresponding author: Dr. Asma Khan (asmazeb26@yahoo.com)
Author roles: Khan DA: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project
Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review &
Editing; Hakim DZ: Conceptualization, Formal Analysis; Waheed DA: Formal Analysis, Supervision; Abrar DN: Conceptualization,
Visualization, Writing – Review & Editing
Competing interests: No competing interests were disclosed.
Grant information: The author(s) declared that no grants were involved in supporting this work.
Copyright: © 2024 Khan DA et al. This is an open access article distributed under the terms of the Creative Commons Attribution License
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite this article: Khan DA, Hakim DZ, Waheed DA and Abrar DN. Impact of CYP3A4 rs2242480 polymorphisms on Imatinib
HPLC determined trough concentration and response in Chronic Myeloid Leukaemia in Pakistani patients [version 1; peer
review: 1 approved with reservations, 1 not approved] F1000Research 2024, 13:310 https://doi.org/10.12688/f1000research.146356.1
First published: 22 Apr 2024, 13:310 https://doi.org/10.12688/f1000research.146356.1
restriction fragment length polymorphism technique was used to
identify the alleles. The results were analyzed using Statistical Package
for Social Sciences (SPSS) version 22.0.
Results
The imatinib concentration in patients with the homozygous wild
allele CC of rs2242480 was higher(1298ng/ml) as compared with the
mutant homozygous TT allele (489ng/ml) or heterozygous allele
CT(873ng/ml)
Conclusion
There was a significant association between imatinib trough levels
and CYP3A4 polymorphism, and trough concentration was found to
be lower in patients with the TT or CT variant of rs2242480 than in
patients with the CC genotype.