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Erschienen in:

01.07.2014 | Original Article

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

verfasst von: Ali-Akbar Golabchifar, Saeed Rezaee, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Nahid Mobarghei Dinan, Mohammad-Reza Rouini

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2014

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Abstract

Purpose

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.

Methods

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.

Results

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 %.

Conclusions

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.

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Titel: Population pharmacokinetics of imatinib in Iranian patients with chronic-phase chronic myeloid leukemia
verfasst von: Ali-Akbar Golabchifar
Saeed Rezaee
Ardeshir Ghavamzadeh
Kamran Alimoghaddam
Nahid Mobarghei Dinan
Mohammad-Reza Rouini
Publikationsdatum: 01.07.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2473-1

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