Effects of methimazole on the elimination of irinotecan
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.
|Keywords||CYP3A, Diarrhea, Drug interaction, Irinotecan, Methimazole, SN-38, UGT1A|
|Persistent URL||dx.doi.org/10.1007/s00280-010-1414-x, hdl.handle.net/1765/33889|
|Journal||Cancer Chemotherapy and Pharmacology|
van der Bol, J.M, Visser, T.J, Loos, W.J, de Jonge, M.J.A, Wiemer, E.A.C, van Aken, M.O, … Mathijssen, A.H.J. (2011). Effects of methimazole on the elimination of irinotecan. Cancer Chemotherapy and Pharmacology, 67(1), 231–236. doi:10.1007/s00280-010-1414-x