Related Experiment Video
Updated: May 29, 2026

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Capecitabine-phenytoin interaction is dose dependent with an unexpected time course
Michael Privitera1, Felipe de Los Ríos la Rosa
1Department of Neurology, University of Cincinnati Health Science Center, Ohio 45267-0525, USA. privitmd@ucmail.uc.edu
Abstract:
The main objective of this study was to further analyze the drug interaction between capecitabine and phenytoin with special emphasis on magnitude, timing, and the dose effect. A single patient had multiple phenytoin levels at various doses of capecitabine. Phenytoin levels were subjected to analysis of variance and the dose effect was approached using a multiple comparison test. All phenytoin levels meeting the criteria for steady state were subjected to box plot analysis. Analysis of 35 phenytoin levels over a 25-month period demonstrated a statistically significant interaction between the medications. The interaction onset was delayed by 4 weeks and persisted up to 9 weeks after capecitabine dose increases or decreases. The magnitude of interaction was directly proportional to the capecitabine dosage. We concluded that capecitabine caused a marked increase in phenytoin levels that was capecitine dose dependent, with a delayed time course not predicted by phenytoin kinetics, suggesting a novel interaction mechanism. The magnitude and complexity of this interaction suggest that alternate antiepileptic medications should be used in combination with capecitabine.
Related Concept Videos
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Chronopharmacokinetics: Time-Dependent Pharmacokinetics
Time-dependent pharmacokinetics refers to non-cyclical changes in drug rate processes over a period of time. It can lead to nonlinear pharmacokinetics, where the relationship between drug concentration and time is not proportional. Non-cyclical...
Pharmacokinetic–Pharmacodynamic Relationship: Duration of Dose-Effect Relationship
Time Course of Drug Effect
Pharmacokinetics: Drug–Drug Interactions
Pharmacokinetics: Drug–Food and Drug–Viral Interactions
