Details

Autor(en) / Beteiligte

• van der Bol, Jessica M
• Visser, Theo J
• Loos, Walter J
• de Jong, Floris A
• Wiemer, Erik A. C
• van Aken, Maarten O
• Planting, Andre S
• Schellens, Jan H
• Verweij, Jaap
• Mathijssen, Ron H. J

Titel

Effects of methimazole on the elimination of irinotecan

Ist Teil von

• Cancer chemotherapy and pharmacology, 2011-01, Vol.67 (1), p.231-236

Ort / Verlag

Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag

Erscheinungsjahr

2011

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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.