Factors Affecting Pharmacokinetic Variability of Imatinib Mesylate (Gleevec, STI-571)
2008-04-18
Doctoral Thesis
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Imatinib mesylate, the first tyrosine kinase inhibitor to gain approval by the FDA, remains as a pivotal example of rational drug design. Initially, imatinib was found to target the bcr-abl fusion protein in CML and further targets have subsequently been identified, including c-kit in GIST. Though a great number of studies have elucidated underlying mechanisms to explain emerging resistance to this anti-cancer agent, many cases of resistance remain unexplained. Furthermore, patients exhibit high interindividual variability in imatinib pharmacokinetics, which may contribute to suboptimal drug exposure and response.
Supervisor
(promotor):
The
author
wishes to thank:
Verweij, Prof. Dr. J. (promotor)
Keywords
Automatically Extracted Terms
- imatinib
- cancer
- patient
- abcb 1
- cyp 3a
- pharmacokinetic
- midazolam
- variant
- resistance
- transporter
- polymorphism
- abcg 2
- protein
- plasma
- expression
- genotype
- concentration
- study
- allele
- difference
