Interferences with Measurement of Anticonvulsants

William Clarke, PhD

Contents

1. Introduction

2. Monitoring of Anticonvulsants

3. Interferences with Commonly Measured Anticonvulsants

4. Conclusion

Summary

Anticonvulsant drugs are the frontline therapy for patients with epilepsy. These drugs fit the "profile" of drugs that should be monitored therapeutically where there is a well-defined relationship between blood concentration and pharmacodynamic effects but a lack of good correlation between dose and the serum blood concentration. For many anticonvulsant drugs, a lack of seizure control can occur when blood concentrations are either above or below the optimum therapeutic interval. There are certain clinical situations where anticonvulsant drugs should be monitored, including establishing baseline effective concentrations, evaluating causes for toxicity or lack of efficacy, evaluating non-compliance versus loss of efficacy, minimizing side effects, and evaluating serum levels when the therapeutic regimen is changed. There are a wide variety of assays available for measuring blood concentrations of anticonvulsants. For chromatographic methods (including those coupled to mass spectrometry), potential interferences come from serum components and other drugs with extraction, or co-eluting substances during chromatography. Antibody-based methods for measurement of drug concentrations allow for an automated, simple analyses of drugs; however, a different source for assay interference must be considered, because cross-reactivity of drugs (or metabolites) with similar structural epitopes must be considered.

Key Words: Anticonvulsants; phenytoin; carbamazepine; valproic acid; Phenobarbital.

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