methimazole and Colorectal-Neoplasms

To study the possible pharmacokinetic and pharmacodynamic interactions between irinotecan and methimazole.. 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).. 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.. 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.

Topics: Antineoplastic Agents, Phytogenic; Antithyroid Agents; Camptothecin; Colorectal Neoplasms; Drug Interactions; Glucuronides; Glucuronosyltransferase; Graves Disease; Humans; Irinotecan; Male; Methimazole; Middle Aged