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Drug Metabolism and Disposition Fast Forward
First published on June 28, 2007; DOI: 10.1124/dmd.106.014043

0090-9556/07/3510-1721-1724$20.00
DMD 35:1721-1724, 2007

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SHORT COMMUNICATION

Influence of Short-Term Use of Dexamethasone on the Pharmacokinetics of Ifosfamide in Patients

Svenja Kristin Brüggemann, Sonja Pfäffle, Stefan Oliver Peters, and Thomas Wagner

Department of Internal Medicine, Section of Hematology/Oncology, University of Lübeck, Lübeck, Germany

Dexamethasone induces the hepatic cytochrome P450 3A and, therefore, is predicted to change the pharmacokinetics, activities, and side effects of drugs metabolized by cytochrome P450 3A. The aim of this study was to determine whether the pharmacokinetics of the cytochrome P450 3A-dependent oxazaphosphorine cytostatic drug ifosfamide is influenced by short-term antiemetic use of dexamethasone in patients. The peak concentration and area under the curve (AUC) were determined for the parent compound and the metabolites 4-hydroxyifosfamide and chloracetaldehyde in eight patients who received two cycles of ICE chemotherapy (ifosfamide 5 g/m2 day 1, carboplatin 300 mg/m2 day 1, etoposide 100 mg/m2 days 1-3). One cycle included concomitant administration of dexamethasone (40 mg over 30 min, 16 h and 1 h before chemotherapy), whereas the other did not. The half-lives of ifosfamide, 4-hydroxyifosfamide, and chloracetaldehyde were shorter with concomitant administration of dexamethasone, but the differences were not statistically significant. In addition, there were no significant differences in the ifosfamide and active 4-hydroxyifosfamide peak concentrations and AUCs when dexamethasone was included. After dexamethasone administration, the chloracetaldehyde peak concentration was slightly increased by 1.5-fold and the AUC by 1.3-fold; however, these increases were not statistically significant. In conclusion, dexamethasone comedication in ICE chemotherapy did not change the ifosfamide pharmacokinetics. Thus, dexamethasone can be used safely as an antiemetic drug in ifosfamide chemotherapy.

Address correspondence to: Thomas Wagner, Department of Internal Medicine, Section of Hematology/Oncology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail: wagnerth{at}uni-luebeck.de




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