Effects of Imatinib on Simvastatin in CML Patients
Author Information
Author(s): O'Brien S G, Meinhardt P, Bond E, Beck J, Peng B, Dutreix C, Mehring G, Milosavljev S, Huber C, Capdeville R, Fischer T
Primary Institution: University of Newcastle Medical School, Royal Victoria Infirmary, New Castle, UK
Hypothesis
Coadministration of imatinib could affect the elimination rate of simvastatin.
Conclusion
Coadministration of imatinib significantly increases the exposure to simvastatin, indicating an inhibition of CYP3A4-mediated metabolism.
Supporting Evidence
- Imatinib increased the mean Cmax value of simvastatin two-fold.
- The AUC(0–∞) value of simvastatin increased three-fold when given with imatinib.
- The mean half-life of simvastatin was prolonged from 1.4 to 2.7 hours with imatinib.
- 70% of patients reported mild to moderate adverse events.
- No deaths occurred during the study.
- Only one patient experienced a grade 3 adverse event not related to the study drugs.
Takeaway
When patients take imatinib and simvastatin together, the amount of simvastatin in their blood can increase a lot, which might cause more side effects.
Methodology
An open-label, nonrandomised, one-sequence study evaluating simvastatin plasma concentration vs time profiles after coadministration with imatinib.
Limitations
The study design allows only limited interpretation of the effects of simvastatin on plasma levels of imatinib.
Participant Demographics
20 adult patients with chronic myeloid leukaemia, 10 male and 10 female, mean age 50.5 years.
Statistical Information
P-Value
p<0.001
Confidence Interval
(0.80, 1.25)
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
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