title: Effects of methimazole on the elimination of irinotecan.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medical Oncology, Erasmus MC University Hospital, Daniel den Hoed Cancer Center, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: van der Bol
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Loos
authors.forename: Floris A
authors.initials: FA
authors.lastname: de Jong
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
authors.forename: Maarten O
authors.initials: MO
authors.lastname: van Aken
authors.forename: Andre S
authors.initials: AS
authors.lastname: Planting
authors.forename: Jan H
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013956:Antithyroid Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy; D004347:Drug Interactions; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism; D006111:Graves Disease / Q000150:complications / Q000188:drug therapy; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008713:Methimazole / Q000494:pharmacology*; D008875:Middle Aged; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013956:Antithyroid Agents; D002166:Camptothecin; D020719:Glucuronides; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D008713:Methimazole; D000099148:UGT1A1 Enzyme