A Bioequivalence Study With Pharmacokinetic Endpoints for Azithromycin Eye Drops

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Drug Delivery Systems

Background:

• Azithromycin eye drops utilize bioadhesive ocular drug-delivery systems for simplified dosing.
• Evaluating generic ophthalmic formulations is crucial for therapeutic equivalence.

Purpose of the Study:

• To compare pharmacokinetic properties and assess bioequivalence between a novel generic azithromycin eye drop and a branded formulation.
• To determine if the generic formulation offers comparable drug exposure in tears.

Main Methods:

• An open-label, single-dose, randomized, crossover, sparse-sampling ocular bioequivalence study was performed on 48 healthy Chinese volunteers.
• Tear samples were collected over 36 hours and analyzed using liquid chromatography-tandem mass spectrometry.
• Pharmacokinetic parameters were calculated using noncompartmental analysis, with bioequivalence assessed via nonparametric bootstrap for 90% confidence intervals.

Main Results:

• The 90% confidence intervals for the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ fell within the 80%-125% bioequivalence range.
• No moderate-to-severe adverse events were reported for either the test or reference azithromycin eye drop formulations.
• Bioequivalence was successfully demonstrated between the generic and branded azithromycin eye drops.

Conclusions:

• The newly developed generic azithromycin eye drop is bioequivalent to the branded formulation.
• The sparse-sampling design combined with bootstrapping is an effective methodology for ophthalmic drug bioequivalence studies.
• This generic formulation provides a safe and therapeutically equivalent option for azithromycin ophthalmic treatment.