Diphenylhydantoin and primidone in tears

Area of Science:

• Pharmacokinetics and Drug Monitoring
• Clinical Chemistry
• Neuropharmacology

Background:

• Epilepsy management requires therapeutic drug monitoring.
• Accurate measurement of antiepileptic drugs (AEDs) in various biological matrices is crucial.
• Diphenylhydantoin (PHT) and primidone (PRM) are commonly prescribed AEDs.

Purpose of the Study:

• To compare the concentrations of PHT and PRM in plasma, tears, saliva, and cerebrospinal fluid (CSF).
• To evaluate the correlation of PHT and PRM levels in different body fluids with plasma concentrations.
• To assess the utility of non-invasive fluid sampling for AED monitoring.

Main Methods:

• Quantitative determination of PHT and PRM using the EMIT (Enzyme Multiplied Immunoassay Technique).
• Analysis of drug concentrations in plasma, tears, saliva, and CSF samples from epileptic patients.
• Statistical analysis to assess correlations between drug levels in different biological fluids.

Main Results:

• PHT concentrations in tears showed a stronger correlation with plasma and CSF levels compared to saliva.
• PRM concentrations exhibited significant interindividual variability across plasma, tears, saliva, and CSF.
• Protein binding and half-life variations contribute to PRM's interindividual pharmacokinetic differences.

Conclusions:

• Tear fluid may serve as a viable alternative matrix for monitoring PHT levels, offering better correlation than saliva.
• PRM's complex pharmacokinetics, characterized by high interindividual variability, necessitate careful monitoring across multiple biological fluids.
• These findings have implications for optimizing therapeutic drug monitoring strategies for PHT and PRM in epilepsy patients.