Therapeutic drug monitoring of imatinib for chronic myeloid leukemia patients in the chronic phase.

Imatinib is approved as a first-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia (CML). Because of the variability in imatinib exposure among patients, therapeutic drug monitoring to maintain a plasma threshold level of about 1,000 ng/ml would be beneficial during imatinib therapy. Imatinib pharmacokinetics are influenced by body weight, comedication and pharmacogenetic factors, and the drug is excreted into the bile by the breast cancer resistance protein (ABCG2 gene). To attain the plasma threshold of approximately 1,000 ng/ml, the daily dose for patients with the ABCG2 421C/C genotype should be 400 mg; for patients with the 421C/A or 421A/A genotype, the dose should be 300 mg. Knowledge of the ABCG2 421 genotype could be useful when making dosing decisions aimed at achieving the optimal imatinib exposure. A therapeutic drug monitoring service should be routinely provided to CML patients taking imatinib. For CML patients who have an imatinib trough level of 1,000 ng/ml but lack a sufficient clinical response, switching to another tyrosine kinase inhibitor is recommended.