Flow-dependent salivary primidone levels in epileptic children

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Analytical Chemistry

Background:

• Primidone is an anticonvulsant medication used in epilepsy treatment.
• Monitoring drug levels is crucial for optimizing therapeutic efficacy and minimizing toxicity.
• Salivary drug levels offer a non-invasive alternative to serum monitoring.

Purpose of the Study:

• To compare primidone levels in resting and flow-stimulated saliva with serum levels.
• To investigate the correlation between salivary flow rate and primidone saliva/serum ratios.
• To assess the suitability of saliva for therapeutic drug monitoring of primidone.

Main Methods:

• Collected resting and flow-stimulated saliva samples from 36 epileptic children on primidone therapy.
• Measured primidone concentrations in saliva and corresponding serum samples.
• Analyzed correlations between saliva I, saliva II, serum levels, and salivary flow rates.

Main Results:

• High correlations were observed between primidone levels in resting saliva (saliva I) and flow-stimulated saliva (saliva II) (r=0.97).
• Primidone levels were significantly lower in saliva II (-38%) compared to saliva I (p<0.001).
• Saliva/serum ratios for primidone were higher in resting saliva (1.115) than in stimulated saliva (0.7), negatively correlating with salivary flow rate.

Conclusions:

• Saliva is a suitable matrix for monitoring primidone levels in epileptic children.
• Standardized sample collection is essential due to variations between resting and stimulated saliva.
• The decrease in saliva/serum ratio with increased flow suggests limited drug permeation, possibly due to low lipid solubility.