Effects of methimazole on the elimination of irinotecan

Jessica Bol, Theo Visser, Walter Loos, FA (Floris) de Jong, Erik Wiemer, MO van Aken, AST Planting, JH Schellens, Jaap Verweij, RHJ Mathijssen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)231-236
Number of pages6
JournalCancer Chemotherapy & Pharmacology
Issue number1
Publication statusPublished - Jan 2011

Research programs

  • EMC MM-01-39-03
  • EMC MM-03-86-08


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