Imatinib mesylate (IM) is the gold standard for treatment of Chronic Myeloid
Leukemia (CML). This study aimed to gain more knowledge of the altered PK,
pharmacogenetic factors, and gene expression leading to variable IM levels.
Fifty patients with chronic phase-CML were enrolled in this study and divided as
25 responders and 25 non-responders (patients are directly recruited after
response assessment). HPLC/MS/MS was used to determine trough
and peak concentration of imatinib and N-desmethyl imatinib in the blood.
PCR-RFLP technique was used to detect IDH1 gene mutation (R132). The median
value of IM trough level was significantly higher, the P/T ratio was
significantly lower and the α-1-acid glycoprotein (AGP) was
significantly higher among responders compared to non-responders
(P=0.007, 0.009 and 0.048, respectively). Higher N-desmethyl imatinib
peak plasma concentration was observed with low mRNA expression of ABCG2 and
OCT1 (P=0.01 and 0.037, respectively). IDH1 R132 gene mutation was
associated with a significant increase in toxicities (P=0.028). In
conclusion, IM trough level, P/T ratio and AGP was significantly higher
in responders. In addition, ABCG2 and OCT1 gene expression may affect the
interindividual PK variation. Although a prospective study with a larger patient
population is necessary to validate these findings. IDH1 mutation is a predictor
of increased toxicity with IM treatment.