Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

Population pharmacokinetics of imatinib in Iranian patients with chronic-phase chronic myeloid leukemia

(2014) Population pharmacokinetics of imatinib in Iranian patients with chronic-phase chronic myeloid leukemia. CANCER CHEMOTHERAPY AND PHARMACOLOGY. pp. 85-93.

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We evaluated the population pharmacokinetics (PPK) and exposure-response relationship of imatinib mesylate in Iranian patients with chronic myeloid leukemia (CML).This study was designed to assess steady state (SS) imatinib trough concentrations (C-min) and pharmacokinetics parameters of imatinib in patients with CML in chronic phase after at least 12-month treatment. Plasma concentrations from a randomized controlled trial consist of 61 patients who received oral imatinib at doses ranged between 300 and 800 mg in various dosing interval, which were quantified using a validated reversed-phase high-performance liquid chromatographic method with UV detection method on different occasions at SS and evaluated using PPK model. A one-compartment model with zero-order absorption and a lag time was sufficient in describing the concentration-time profile. Inter-individual variability (IIV) was modeled for all parameters. Oral clearance (CL/F) and the volume of distribution (V/F) were estimated to 10.8 L/h with 30 % IIV and 265 L with 53 % IIV, respectively. Inter-occasion variability (IOV) was included in CL/F (17 %) and V/F (22 %).The proportional residual error of the model was 8 %. Simulation analysis from individual parameters shows exposure to imatinib is highly variable among patients. Imatinib trough plasma levels < 1,257 ng/mL were associated with lower rates of major molecular response. Because of the wide IIV compared with IOV with imatinib in our study, trough levels may play a role in investigating instances of suboptimal response.

Item Type: Article
Keywords: Author Keywords:Imatinib; Population pharmacokinetics; Chronic myeloid leukemia; Therapeutic drug monitoring KeyWords Plus:TYROSINE KINASE; MOLECULAR RESPONSES; DRUG DEVELOPMENT; PLASMA-LEVELS; TROUGH LEVEL; INDUSTRY; SAFETY
Page Range: pp. 85-93
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q3
Volume: 74
Number: 1
Publisher: web of science
Depositing User: خانم مریم زرقانی

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