Therapeutic Drug Monitoring (TDM) of Imatinib: Effectiveness of Bayesian dose adjustment for CML patients enrolled in the Imatinib Concentration Monitoring (I-COME) study


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Therapeutic Drug Monitoring (TDM) of Imatinib: Effectiveness of Bayesian dose adjustment for CML patients enrolled in the Imatinib Concentration Monitoring (I-COME) study
Title of the conference
Réunion annuelle Société Suisse de Médecine Intensive, Société Suisse d'Infectiologie, Société Suisse d'Hygiène Hospitalière, Société Suisse de Pharmacologie et Toxicologie Cliniques, Communauté Suisse d'intérêts pour soins intensifs, Invité: Société Suisse de Transplantation
Gotta V., Widmer N., Decosterd L.A., Csajka C., Duchosal M.A., Chalandon Y., Heim D., Gregor M., Buclin T.
Lausanne, Suisse, 2-4 septembre 2010
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Issued date
Swiss Medical Forum = Forum Médical Suisse
Introduction: As imatinib pharmacokinetics are highly variable, plasma
levels differ largely between patients under the same dosage. Retrospective
studies in chronic myeloid leukemia (CML) patients showed
significant correlations between low levels and suboptimal response, as
well as between high levels and poor tolerability. Monitoring of trough
plasma levels, targeting 1000 μg/L and above, is thus increasingly
advised. Our study was launched to assess prospectively the clinical
usefulness of systematic imatinib TDM in CML patients. This preliminary
analysis addresses the appropriateness of the dosage adjustment
approach applied in this study, which targets the recommended trough
level and allows an interval of 4-24 h after last drug intake for blood
Methods: Blood samples from the first 15 patients undergoing 1st TDM
were obtained 1.5-25 h after last dose. Imatinib plasma levels were
measured by LC-MS/MS and the concentrations were extrapolated to
trough based on a Bayesian approach using a population pharmacokinetic
model. Trough levels were predicted to differ significantly from
the target in 12 patients (10 <750 μg/L; 2 >1500 μg/L along with poor
tolerance) and individual dose adjustments were proposed. 8 patients
underwent a 2nd TDM cycle. Trough levels of 1st and 2nd TDM were
compared, the sample drawn 1.5 h after last dose (during distribution
phase) was excluded from the analysis.
Results: Individual dose adjustments were applied in 6 patients.
Observed concentrations extrapolated to trough ranged from 360 to
1832 μg/L (median 725; mean 810, CV 52%) on 1st TDM and from
720 to 1187 μg/L (median 950; mean 940, CV 18%) on 2nd TDM cycle.
Conclusions: These preliminary results suggest that TDM of imatinib
using a Bayesian interpretation is able to target the recommended
trough level of 1000 μg/L and to reduce the considerable differences in
trough level exposure between patients (with CV decreasing from 52%
to 18%). While this may simplify blood collection in daily practice, as
samples do not have to be drawn exactly at trough, the largest possible
interval to last drug intake yet remains preferable to avoid sampling
during distribution phase leading to biased extrapolation. This encourages
the evaluation of the clinical benefit of a routine TDM intervention
in CML patients, which the randomized Swiss I-COME trial
aims to.
Create date
01/12/2010 10:57
Last modification date
20/08/2019 15:44
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