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Factors affecting the bioavailability of phenytoin
International Journal of Clinical Pharmacology and Biopharmacy
|February 1, 1977
Summary
Bioavailability of phenytoin (DPH) formulations varied significantly. Micronized DPH suspension showed highest bioavailability, while large particle size tablets had the lowest, highlighting formulation
Area of Science:
- Pharmacokinetics
- Pharmaceutical Sciences
- Drug Bioavailability
Background:
- Phenytoin (DPH) is a widely used antiepileptic drug.
- Variability in DPH product bioavailability can impact therapeutic efficacy.
- Understanding formulation effects on DPH absorption is crucial.
Purpose of the Study:
- To compare the bioavailability of seven different phenytoin (DPH) formulations.
- To investigate the relationship between in vitro dissolution and in vivo DPH bioavailability.
- To identify key formulation factors influencing DPH absorption.
Main Methods:
- Cross-over study design with six healthy volunteers.
- Administration of single 600 mg doses of DPH formulations.
- Determination of bioavailability using Area Under the Serum Concentration-Time Curve (AUC).
- In vitro dissolution rate testing in borate buffer (pH 9).
Main Results:
- Significant differences in DPH bioavailability were observed across formulations.
- Highest bioavailability was achieved with micronized DPH suspension.
- Lowest bioavailability (26% of the highest) was found in DPH tablets with the largest particle size.
- A strong positive correlation (r=0.93) was found between in vitro dissolution rate and in vivo DPH bioavailability.
Conclusions:
- Formulation, particularly particle size, significantly impacts phenytoin bioavailability.
- In vitro dissolution rate is a reliable predictor of in vivo DPH product performance.
- Optimizing formulation factors is essential for consistent DPH absorption and therapeutic outcomes.