Therapeutic drug monitoring · 2014
Plasma and intracellular imatinib concentrations in patients with chronic myeloid leukemia.
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De Francia Silvia, DʼAvolio Antonio, Ariaudo Alessandra, Pirro Elisa, Piccione Francesca, Simiele Marco, Fava Carmen, Calcagno Andrea, Di Perri Giovanni, Saglio Giuseppe
Аннотация
BACKGROUND: Imatinib (Gleevec, STI-571), a 2-phenylaminopyrimidine-type competitive inhibitor of Bcr-Abl kinase, is the current frontline therapy for patients with chronic myeloid leukemia, and it induces durable responses and prolonging event-free and progression-free survival. Monitoring imatinib trough plasma concentration is a simple and rapid way to determine if the drug exposure exceeds the clinical efficacy threshold (1 mcg/mL). Because the target enzyme is located within cells, adequate drug intracellular concentrations are needed to inhibit its function.
METHODS: Chromatographic methods were used to quantify imatinib concentrations in both plasma and peripheral blood mononuclear cells collected from adult patients with chronic myeloid leukemia at the Department of Hematology. Samples were collected at steady state, and trough concentrations (24 ± 2 hours after last drug intake) were evaluated. Associations between variables were tested using the Pearson test; results are presented as mean (±SD).
RESULTS: Thirty-five samples from 24 patients were collected; patients were mainly men (16, 66.7%), aged 60 years old (±13.1) and with a body mass index of 24.8 (±4.4). A positive and significant correlation (r = 0.203; P = 0.027) was found between imatinib plasma and intracellular concentrations.
CONCLUSIONS: The observed correlation between plasma and intracellular imatinib concentrations suggests that they may be used to monitor drug exposure and treatment efficacy.
METHODS: Chromatographic methods were used to quantify imatinib concentrations in both plasma and peripheral blood mononuclear cells collected from adult patients with chronic myeloid leukemia at the Department of Hematology. Samples were collected at steady state, and trough concentrations (24 ± 2 hours after last drug intake) were evaluated. Associations between variables were tested using the Pearson test; results are presented as mean (±SD).
RESULTS: Thirty-five samples from 24 patients were collected; patients were mainly men (16, 66.7%), aged 60 years old (±13.1) and with a body mass index of 24.8 (±4.4). A positive and significant correlation (r = 0.203; P = 0.027) was found between imatinib plasma and intracellular concentrations.
CONCLUSIONS: The observed correlation between plasma and intracellular imatinib concentrations suggests that they may be used to monitor drug exposure and treatment efficacy.