A comparative clarithromycin bioavailability study: determination of clarithromycin and 14-(R)-hydroxyclarithromycin...

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Clinical Pharmacology

Background:

• Bioequivalence studies are crucial for generic drug approval.
• Clarithromycin (CLA) is a widely used antibiotic.
• Understanding drug absorption under different conditions is essential.

Purpose of the Study:

• To conduct a comprehensive bioequivalence analysis of clarithromycin (CLA) and its metabolite 14-(R)-hydroxyclarithromcin (14R).
• To evaluate bioequivalence under both fasting and fed states using a validated analytical method.
• To determine if the generic clarithromycin product is comparable to the reference product.

Main Methods:

• Two separate bioequivalence studies were conducted in non-smoking subjects (n=40 fasting, n=18 fed).
• A crossover trial design assessed the comparative bioavailability of a 500 mg generic clarithromycin tablet against the reference product.
• High-performance liquid chromatography (HPLC) coupled with mass spectrometry was used for analysis.

Main Results:

• The analytical method achieved a low limit of quantitation (LLOQ) of 11 ng/ml for both analytes.
• The generic clarithromycin product met bioequivalence criteria (common mean geometric ratio and 90% confidence limits) compared to the reference product in both fasting and fed studies.
• Intra-subject variabilities for AUC and Cmax were within acceptable ranges (< or = 21% and < or = 26%, respectively).

Conclusions:

• The 500 mg generic clarithromycin tablet is bioequivalent to Biaxin Filmtab under both fasting and fed conditions.
• Bioequivalence was confirmed for both clarithromycin (CLA) and its metabolite 14-(R)-hydroxyclarithromcin (14R).
• Clarithromycin is not classified as a highly variable drug at the 500 mg dose.