Effect of Pharmacogenetics on Imatinib Plasma Level and Response

Imatinib, the tyrosine kinase inhibitor, is used for treatment of Philadelphia positive chronic myeloid leukemia. Despite its efficacy and favorable pharmacokinetic profile, there is a large inter-individual variability in imatinib plasma concentrations, which may lead to treatment failure and disease progression. Polymorphisms in genes related to absorption, distribution, metabolism and excretion of imatinib may affect the bioavailability and consequently the response to the drug. The study aims to investigate the possible effect of genetic polymorphisms in certain metabolizing enzymes \[CYP3A5\*3 (rs776746), CYP2C8\*3 (rs11572080 and rs10509681)\] and membrane transporters \[ABCB1 2677G\>T/A (rs2032582) and SLC22A1 1222A \> G (rs628031)\] by PCR on the plasma level (by HPLC-UV) and molecular response (MMR) of imatinib in patients with CML. The study also aims to provide CML patients with a personalized treatment option, thereby probably improving the response and reducing the side effects.