Effect of antacids on phenytoin bioavailability

Area of Science:

• Pharmacokinetics
• Drug Interactions
• Gastroenterology

Background:

• Phenytoin is a widely used antiepileptic drug.
• Antacids are commonly used for gastrointestinal issues, such as peptic ulcers.
• Potential interactions between antacids and phenytoin absorption are not fully understood.

Purpose of the Study:

• To investigate the impact of three common antacids on the oral bioavailability of phenytoin.
• To assess whether aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), or aluminum hydroxide-magnesium trisilicate (AHMT) affect phenytoin absorption.

Main Methods:

• A randomized crossover study involving eight subjects.
• Administration of a single 600-mg oral dose of phenytoin alone and with each of the three antacids (AMH, CC, AHMT).
• Measurement of phenytoin bioavailability using area under the curve (AUC) and urinary metabolite (HPPH) levels.

Main Results:

• Aluminum-magnesium hydroxide (AMH) and calcium carbonate (CC) significantly decreased phenytoin's AUC (p<0.005 and p<0.05, respectively).
• Aluminum hydroxide-magnesium trisilicate (AHMT) showed a similar trend, but without statistical significance (p=0.1).
• Observed significant inter- and intrasubject variability in phenytoin absorption.

Conclusions:

• Concomitant use of AMH and CC with phenytoin can significantly reduce its bioavailability.
• Antacids may alter both the extent and rate of phenytoin absorption.
• Caution is advised for patients taking both antacids and phenytoin concurrently, particularly those on peptic ulcer regimens.