Journal
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Volume 65, Issue 6, Pages 885-892Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2125.2008.03150.x
Keywords
CML; CYP2D6; Glivec; imatinib; metoprolol; pharmacokinetics
Categories
Ask authors/readers for more resources
AIMS To investigate the effect of imatinib on the pharmacokinetics of a CYP2D6 substrate, metoprolol, in patients with chronic myeloid leukaemia (CML). The pharmacokinetics of imatinib were also studied in these patients. METHODS Patients (n = 20) received a single oral dose of metoprolol 100 mg on day 1 after an overnight fast. On days 2-10, imatinib 400 mg was administered twice daily. On day 8, another 100 mg dose of metoprolol was administered 1 h after the morning dose of imatinib 400 mg. Blood samples for metoprolol and alpha-hydroxymetoprolol measurement were taken on study days 1 and 8, and on day 8 for imatinib. RESULTS Of the 20 patients enrolled, six patients (30%) were CYP2D6 intermediate metabolizers (IMs), 13 (65%) extensive metabolizers (EMs), and the CYP2D6 status in one patient was unknown. In the presence of 400 mg twice daily imatinib, the mean metoprolol AUC was increased by 17% in IMs from 1190 to 1390 ng ml(-1) h), and 24% in EMs (from 660 to 818 ng ml(-1) h). Patients classified as CYP2D6 IMs had an approximately 1.8-fold higher plasma metoprolol exposure than those classified as EMs. The oral clearance of imatinib was 11.0 +/- 2.0 l h(-1) and 11.8 +/- 4.1 l h(-1) for CYP2D6 IMs and EMs, respectively. CONCLUSIONS Co-administration of a high dose of imatinib resulted in a small or moderate increase in metoprolol plasma exposure in all patients regardless of CYP2D6 status. The clearance of imatinib showed no difference between CYP2D6 IMs and EMs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available