Effects of methimazole on the elimination of irinotecan |
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Authors: | Jessica M van der Bol Theo J Visser Walter J Loos Floris A de Jong Erik A C Wiemer Maarten O van Aken Andre S Planting Jan H Schellens Jaap Verweij Ron H J Mathijssen |
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Institution: | 1. Department of Medical Oncology, Erasmus MC University Hospital, Daniel den Hoed Cancer Center, ‘s Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands 2. Department of Endocrinology, Erasmus MC, Rotterdam, The Netherlands 3. Division of Clinical Pharmacology, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands 4. Science Faculty, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
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Abstract: | 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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