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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2011

Open Access 01-01-2011 | Short Communication

Effects of methimazole on the elimination of irinotecan

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2011

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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.
Appendix
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Metadata
Title
Effects of methimazole on the elimination of irinotecan
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
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-010-1414-x

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