Phenytoin bioavailability assessed by steady state serum concentrations.

Area of Science:

• Pharmacokinetics
• Drug Formulation
• Clinical Pharmacology

Background:

• Phenytoin sodium formulations can vary in bioavailability.
• Changes in bioavailability affect steady-state serum concentrations.
• Assessing these changes is crucial for patient treatment.

Purpose of the Study:

• To evaluate the impact of a new phenytoin sodium formulation on steady-state serum concentrations.
• To compare the bioavailability of old and new phenytoin formulations.
• To determine the clinical significance of formulation changes on drug efficacy.

Main Methods:

• Comparison of phenytoin serum levels in neurosurgical patients on old (1980) vs. new (1983) formulations.
• Analysis of routine therapeutic drug monitoring data for ambulatory patients on the new formulation (1984).
• Estimation of phenytoin elimination rates and Michaelis-Menten constants from dose-concentration data.

Main Results:

• The new formulation resulted in significantly higher phenytoin serum concentrations (16.1 vs. 10.9 µg/ml at 400 mg/day; 12.1 vs. 6.9 µg/ml at 300 mg/day).
• The maximum elimination rate of phenytoin was significantly higher on the old formulation.
• The proportion of subtherapeutic phenytoin levels decreased substantially with the new formulation (from 85% to 45% at 300 mg/day).

Conclusions:

• The new phenytoin sodium formulation demonstrates increased bioavailability compared to the old one.
• Steady-state serum concentrations are a reliable indicator for assessing bioavailability changes in drugs with capacity-limited metabolism, like phenytoin.
• Formulation improvements can enhance therapeutic efficacy and reduce subtherapeutic drug levels.