Bioavailability studies with etodolac in dogs and man.

Area of Science:

• Pharmacokinetics
• Drug Formulation
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Background:

• Etodolac is a novel non-steroidal anti-inflammatory agent.
• Understanding its bioavailability is crucial for effective therapeutic use.
• Factors influencing drug absorption and disposition require thorough investigation.

Purpose of the Study:

• To evaluate the impact of formulation, particle size, food, antacids, and antiulcer agents on etodolac bioavailability.
• To assess the effects of dosage regimen and repetitive dosing on etodolac bioavailability.
• To compare the bioavailability of different etodolac formulations in dogs and humans.

Main Methods:

• Bioavailability studies were conducted in dogs and humans.
• Evaluated effects of capsule, tablet, and solution formulations.
• Assessed influence of micronized vs. regular particle sizes.
• Investigated coadministration with food, magaldrate (antacid), and sucralfate (antiulcer agent).
• Determined effects of single vs. divided (b.i.d.) and repetitive (7-day) dosing regimens.

Main Results:

• Capsule and tablet formulations of micronized etodolac demonstrated bioavailability (AUC) equivalent to the etodolac solution in humans.
• Etodolac absorption from tablets and capsules was rapid, with minor changes in Cmax and tmax compared to the solution.
• Micronized and regular etodolac formulations showed similar bioavailability (AUC) in both species, with parallel minor changes in Cmax and tmax.
• Food intake did not affect etodolac bioavailability in dogs but delayed absorption.
• Coadministration with magaldrate or sucralfate did not alter etodolac bioavailability in dogs, though sucralfate reduced Cmax.
• Etodolac can be administered as a single or divided dose in humans without bioavailability loss.
• No etodolac accumulation was observed with repetitive dosing for 7 days.

Conclusions:

• Etodolac exhibits consistent bioavailability across various formulations and particle sizes.
• Food, antacids, and antiulcer agents generally do not impact etodolac bioavailability.
• Etodolac can be administered flexibly regarding dosage regimen and repetitive dosing without compromising bioavailability or causing accumulation.