Pharmacokinetics and Bioequivalence of Two Formulations of Azithromycin Tablets: A Randomized, Single Dose, 3-Period Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Abstract

Background Azithromycin is the first azalidic antibiotic that is related to the macrolide family of antibiotics. This study was conducted to compare the bioequivalence of two azithromycin tablets under fasting and fed conditions in healthy Chinese volunteers. Methods The study was a single-dose, reference-replicated, 3-period crossover trial. A total of 72 healthy subjects (36 subjects in the fasting state study and 36 subjects in the fed study) were enrolled in the study and were randomized to treatment. After the administration of a single oral dose of a 250 mg generic azithromycin tablet (test) or branded azithromycin tablet (reference), blood samples were collected at specific time intervals from 0 to 120 hours. The plasma concentrations of azithromycin were measured by high-performance liquid chromatography–tandem mass spectrometry (HPLC‒MS/MS). Non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Adverse events were also recorded. Results In fasting test, the either reference-scaled average bioequivalence (RSABE) approach was used to evaluate the bioequivalence of maximum plasma concentration (Cmax) (withinsubject standard deviation, SWR>0.294), while average bioequivalence (ABE) method was used to evaluate the bioequivalence of area under the cocentration-time curve from time 0 to the time of the last measurable plasma concentration (AUC0 − t ) and area under the cocentration-time curve from time 0 extrapolated to infinity (AUC0−∞) (SWR<0.294). The geometric mean ratio (GMR) of the test/reference for Cmax was 106.49%, and the 95% upper confidence bound was < 0. For AUC0 − t and AUC0−∞ comparisons, GMRs were 103.34% and 101.28%, and the 90% CIs of the test/reference were 95.90%-111.35%, 94.85%-108.15%, respectively. In fed test, the RSABE approach was used to evaluate the bioequivalence of Cmax (SWR>0.294), while ABE approach was used to evaluate the bioequivalence of AUC0 − t and AUC0−∞ (SWR<0.294). The GMRs for Cmax was 99.80%, while the 95% upper confidence bound value was < 0. For AUC0 − t and AUC0−∞ comparisons, GMRs were 97.07% and 98.15%, and the 90% CIs of the test/reference were 90.02%-104.68%, 90.66%-106.25%, respectively. All adverse events were mild and transient. Conclusions The trial demonstrated that the test and the reference azithromycin tablets were bioequivalent and well tolerated in Chinese volunteers under fasting and fed conditions. Trial Registration: Clinicaltrials, ChiCTR2300071630 (retrospectively registered in 19/05/2023).