2011
Effects of methimazole on the elimination of irinotecan
Publication
Publication
Cancer Chemotherapy and Pharmacology , Volume 67 - Issue 1 p. 231- 236
Purpose: To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole. Methods: A patient treated for colorectal cancer with single agent irinotecan received methimazole co-medication for Graves' disease. Irinotecan pharmacokinetics and side effects were followed during a total of four courses (two courses with and two courses without methimazole). Results: Plasma concentrations of the active irinotecan metabolite SN-38 and its inactive metabolite SN-38-Glucuronide were both higher (a mean increase of 14 and 67%, respectively) with methimazole co-medication, compared to irinotecan monotherapy. As a result, the mean SN-38 glucuronidation rate increased with 47% during concurrent treatment. Other possible confounding factors did not change over time. Specific adverse events due to methimazole co-treatment were not seen. Conclusions: Additional in vitro experiments suggest that these results can be explained by induction of UGT1A1 by methimazole, leading to higher SN-38G concentrations. The prescribed combination of these drugs may lead to highly toxic intestinal SN-38 levels. We therefore advise physicians to be very careful in combining methimazole with regular irinotecan doses, especially in patients who are prone to irinotecan toxicity.
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doi.org/10.1007/s00280-010-1414-x, hdl.handle.net/1765/33889 | |
Cancer Chemotherapy and Pharmacology | |
Organisation | Erasmus MC: University Medical Center Rotterdam |
van der Bol, J., Visser, T., Loos, W., de Jonge, M., Wiemer, E., van Aken, M., … Mathijssen, R. (2011). Effects of methimazole on the elimination of irinotecan. Cancer Chemotherapy and Pharmacology, 67(1), 231–236. doi:10.1007/s00280-010-1414-x |