title: No clinical evidence for performing trough plasma and intracellular imatinib concentrations monitoring in patients with chronic myelogenous leukaemia.
abstract: This multicentre study focused on monitoring imatinib mesylate (IMA) trough plasma (Ctrough ) and intracellular (IMA Cintrac ) concentrations in 228 chronic myelogenous leukaemia patients. The median of measured IMA Ctrough in our patient group was 905.8 ng ml (range: 27.7-4628.1 ng/ml). We found a correlation between IMA Ctrough and alpha 1-acid glycoprotein plasma concentrations (rS = 0.42; p < 0.001). All other analysed parameters revealed only weak (gender, dose of IMA per kg) or not significant (age, albumin, creatinine plasma concentration or body mass index) impact on measured IMA Ctrough. The IMA Ctrough decreased during the first 6 months and significantly increased later during treatment. The IMA Ctrough at the first month of therapy did not differ between patients with and without an optimal response at the 12th (p = 0.724) and 18th month (p = 0.135) of therapy. There were no significant differences in medians of IMA Ctrough between both groups measured during the first year of treatment. The IMA Cintrac during the first month were not different between patients with and without an optimal response at the 6th (p = 0.273) and the 12th month (p = 0.193) of therapy. Our data obtained from real life clinical practice did not find a benefit of routine and regular IMA Ctrough nor IMA Cintrac therapeutic drug monitoring in chronic myelogenous leukaemia patients or for subsequent adjustments of the IMA dose based on these results. Moreover, actual alpha 1-acid glycoprotein plasma concentration should be used for proper interpretation of IMA Ctrough results.
authors: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic; CEITEC - Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors: Zdenek
authors: Z
authors: Racil
authors: Filip
authors: F
authors: Razga
authors: Hana
authors: H
authors: Klamova
authors: Jaroslava
authors: J
authors: Voglova
authors: Petra
authors: P
authors: Belohlavkova
authors: Ludmila
authors: L
authors: Malaskova
authors: David
authors: D
authors: Potesil
authors: Jan
authors: J
authors: Muzik
authors: Daniela
authors: D
authors: Zackova
authors: Katerina Machova
authors: KM
authors: Polakova
authors: Zbynek
authors: Z
authors: Zdrahal
authors: Jana
authors: J
authors: Malakova
authors: Jiri
authors: J
authors: Suttnar
authors: Jan
authors: J
authors: Dyr
authors: Jiri
authors: J
authors: Mayer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: CML; cell-associated concentration; imatinib; plasma concentration