Impact of co-administered drugs on drug monitoring of capecitabine in patients with advanced colorectal cancer

Veronika Schreiber; Marie Kitzmueller; Martina Poxhofer; Stefanie Gintersdorfer; Catharina Neudorfer; Maria Lichtneckert; Christian Dittrich; Martin Czejka

Impact of co-administered drugs on drug monitoring of capecitabine in patients with advanced colorectal cancer

Anticancer Res. 2014 Jul;34(7):3371-6.

Authors

Veronika Schreiber¹, Marie Kitzmueller², Martina Poxhofer², Stefanie Gintersdorfer², Catharina Neudorfer³, Maria Lichtneckert⁴, Christian Dittrich⁴, Martin Czejka⁵

Affiliations

¹ Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria veronika.schreiber@univie.ac.at.
² Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
³ Department of Drug and Natural Product Synthesis, University of Vienna, Vienna, Austria.
⁴ Center for Social Medicine, Kaiser Franz-Josef Hospital with Gottfried von Preyer Pediatric Hospital, Hospital Pharmacy, Vienna, Austria.
⁵ Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria.

PMID: 24982342

Abstract

Background: Drug monitoring is a useful tool for obtaining detailed information about the disposition of a drug in an individual patient during chemotherapy. According to the international guidelines, the analytical assay for quantification of a compound in biological samples must be validated. Among a number of parameters, peak purity is an important requirement.

Materials and methods: We analyzed pharmacokinetics in patients who received chemotherapy with capecitabine and up to 10 various co-medications.

Results: Out of seven investigated co-administered drugs, we found evidence that the proton pump inhibitor pantoprazole causes peak interferences with capecitabine during high-performance liquid chromatography analysis. Therefore quantification of capecitabine in plasma samples can be inaccurate.

Conclusion: We recommend an altered time schedule for co-administered drugs or changing the mobile phase used in the assay.

Keywords: Capecitabine; HPLC; interaction; metabolites; pantoprazole; premedication.

MeSH terms

2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
2-Pyridinylmethylsulfinylbenzimidazoles / blood
2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / blood*
Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
Capecitabine
Chromatography, High Pressure Liquid / methods
Colorectal Neoplasms / blood*
Colorectal Neoplasms / drug therapy*
Deoxycytidine / administration & dosage
Deoxycytidine / analogs & derivatives*
Deoxycytidine / blood
Deoxycytidine / pharmacokinetics
Drug Administration Schedule
Drug Interactions
Drug Monitoring / methods*
Floxuridine / blood*
Fluorouracil / administration & dosage
Fluorouracil / analogs & derivatives*
Fluorouracil / blood
Fluorouracil / pharmacokinetics
Humans
Pantoprazole
Proton Pump Inhibitors / administration & dosage
Proton Pump Inhibitors / blood
Proton Pump Inhibitors / pharmacokinetics

Substances

2-Pyridinylmethylsulfinylbenzimidazoles
Proton Pump Inhibitors
Floxuridine
Deoxycytidine
Capecitabine
5'-deoxy-5-fluorocytidine
Pantoprazole
Fluorouracil
doxifluridine