A Reference‐Scaled Average Bioequivalence Study of Azithromycin Tablets Manufactured in China and the United States: An Open‐Label, Randomized, Single‐Dose, 3‐Way Crossover Study in Healthy Chinese Subjects Under Fasted and Fed Conditions

Abstract

Azithromycin (Zithromax) is an azalide antibiotic that binds to the 50S ribosomal subunit of the susceptible organism and thereby interferes with its protein synthesis. An open-label, randomized, single-dose, 3-way crossover bioequivalence study was conducted to compare the rate and extent of absorption of the azithromycin 250-mg tablet manufactured at Pfizer Dalian (China) and that at Pfizer Barceloneta (United States) under fasted and fed conditions in healthy Chinese subjects.This study aimed to support a generic consistency evaluation program,initiated by the National Medical Products Administration, for evaluating the quality and efficacy of the products manufactured in China. In the study, the withinsubject standard deviation for area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fasted condition was <0.294, and the 90%CI for the ratio was within 80% to 125%; the within-subject SDs for serum peak concentration in the fasted condition, area under the serum concentration-time profile from time 0 to 72 hours after dosing in the fed condition, and serum peak concentration in the fed condition, were all >0.294, with the upper confidence bounds being <0.00, and the point estimates of the ratios being within 80% to 125%. The results support the bioequivalence between azithromycin tablets manufactured in China and the United States in fasted and fed conditions, with both tablets showing an acceptable safety/tolerability profile in the studied population.

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

“…Safety evaluation indicated all the AEs were mild and All AEs were dealt with in a timely and appropriate manner and were followed up until the events returned to normal or stabilized. The AEs reported in the our study were increased triglycerides, uricacid, urinary RBC, decreased potassium, and diarrhea, which had been reported in previous studies [10].There was no signi cant difference in the rate of AEs between the test and reference drug groups under fasting as well as fed condition. In short, both formulations of azithromycin showed good tolerance regardless of fast or fed condition in healthy Chinese subjects.…”

“…There were a few studies on the pharmacokinetics and bioequivalence of generic azithromycin formulations, such as tablets [10][11][12], granules [13], capsules [14] and eye drops [15], with the dosages of 250 mg or 500 mg.…”

“…(5) a history of smoking (> 5 cigarettes per day) during the 3 months before screening; (6) had consumed a special diet (including grapefruit, xanthine-containing diet, etc) or other beverages or foods that affect drug absorption,distribution, metabolism, or excretion within 7 days before administration; (7) had donated blood or had massive blood loss (> 400 mL) or participated in another clinical trial within 3 months before the screening; (8) had consumed > 8 cups of tea, coffee, or caffeinated beverages every day in the month before screening; (9) had special dietary requirements and could not follow the diet and corresponding regulations provided; (10) had no pregnancy plans for the following 6 months and voluntarily used effective contraception. (11) female subjects who were lactating or had a positive pregnancy result during the screening period or during the trial; (12) other factors that were inappropriate for participating in the study as determined by the investigator.…”

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

“…The AZI is an antibiotic commonly used to treat various bacterial infections, including skin infections 47 . This part of the study investigated the release characteristics of loaded AZI from the fabricated membranes.…”

Bioequivalence of Two 6‐Mercaptopurine Tablet Formulations in Healthy Fasting Chinese Volunteers

“…Area under the plasma concentration–time curve (AUC) and peak plasma concentration (C max ) were calculated as the metrics for BE using WinNonlin 8.2 (Certara). The average BE (ABE) method 12 was adopted when the C max and/or AUC within‐subject standard deviation (S WR ) of the reference formulation was less than 0.294. BE was accepted if the 90% confidence interval (CI) values of the test formulation AUC and/or C max geometric mean ratio (GMR) fell within 80%–125% of the reference formulation values.…”