title: Imatinib plasma trough levels in chronic myeloid leukaemia: results of a multicentre study CSTI571AIL11TGLIVEC.
abstract: Imatinib has been accepted as frontline treatment for patients with chronic myeloid leukaemia (CML), and patients generally receive doses ranging from 400 to 800 mg/day. Previous studies have demonstrated that maintaining imatinib plasma levels (IMPLs) >1000 ng/mL leads to improved responses and long-term outcomes. However, IMPLs vary among patients because of factors such as drug-drug interactions, adherence, toxicity and differential levels of expression of cellular efflux/influx proteins. In this study, IMPLs were analysed in 191 patients with CML and were compared with achievement of molecular and cytogenetic responses (CyR). IMPLs were also correlated with renal and hepatic dysfunction. Additionally, self-reported adherence was monitored. The median and mean IMPLs were 994 ng/mL and 1070 ± 686 ng/mL, respectively, with 96 patients (50%) achieving plasma levels >1000 ng/mL. Self-reported patient compliance was 98%. Patients who achieved a complete CyR (CCyR) had significantly higher IMPLs (1078 ± 545 ng/mL) than those without CyR (827 ± 323 ng/mL, p = 0.045). When grouped together, patients who achieved a CCyR or partial CyR had significantly higher IMPLs than patients who achieved a minimal CyR or did not achieve a CyR (1066 ng/mL vs 814 ng/mL, p = 0.002). There was no significant difference observed in the IMPLs between patients who achieved molecular responses (n = 177) on treatment (major molecular response, 976 ± 385 ng/mL versus complete molecular response, 1138 ± 809 ng/mL, p = 0.387). Mean IMPLs were similar in patients with or without renal or hepatic impairment. Overall, this study confirmed previous reports that higher IMPLs correlate with clinical responses and demonstrated that imatinib exposure did not differ in patients with or without liver and/or renal dysfunction. The use of IMPL testing and patient diaries may be practical tools for the management of imatinib therapy in patients with CML.
authors.affiliation: Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Koren-Michowitz
authors.forename: Yulia
authors.initials: Y
authors.lastname: Volchek
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Naparstek
authors.forename: Israel
authors.initials: I
authors.lastname: Gavish
authors.forename: Itai
authors.initials: I
authors.lastname: Levi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate