A Bioequivalence Study With Pharmacokinetic Endpoints for Azithromycin Eye Drops

Wu, Feng; Zhao, Xiuli; Guo, Shaojie; Ni, Siyang; Dai, Yinmei; Han, Ying; Ma, Ke; Wang, Yunzhe

doi:10.1002/cpdd.1226

Cited by 3 publications

(1 citation statement)

References 23 publications

(50 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Chen,

Ye,

Mei

et al. 2023

Preprint

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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).

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Section: Discussionmentioning

confidence: 99%

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

Chen,

Ye,

Mei

et al. 2023

Preprint

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

Chen,

Ye,

Mei

et al. 2024

Drugs R D

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Background and Objective Azithromycin is the first azalide antibiotic that is related to the macrolide family of antibiotics. Bioequivalence studies in China are initiated by the National Medical Products Administration (NMPA), which supports a generic consistency evaluation program for ensuring that generic products manufactured in China meet the required standards and provide equivalent therapeutic effects to their reference products. This study aimed to assess the bioequivalence of two azithromycin tablets under both fasting and fed conditions in healthy Chinese volunteers. Methods This was a single-center, open-label, single-dose, randomized, three-way crossover trial with two independent groups (fasting group and fed group). A total of 72 healthy Chinese subjects (36 subjects in the fasting state and 36 subjects in the fed state) were enrolled and randomized to treatment. Blood samples were collected from 0 to 120 h after a single oral dose of a 250-mg generic azithromycin tablet (test, T) or branded azithromycin tablet (reference, R). The plasma concentrations of azithromycin were determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC‒MS/MS). A non-compartmental analysis method was used to estimate the pharmacokinetic parameters. Adverse events were documented. Results In a fasting state, the bioequivalence of maximum plasma concentration ( C max ) was evaluated using the reference-scaled average bioequivalence (RSABE) approach (within-subject standard deviation, S WR > 0.294), and the bioequivalence of area under the concentration–time curve from time 0 to the time of the last measurable plasma concentration (AUC 0– t ) and area under the concentration–time curve from time 0 extrapolated to infinity (AUC 0– ∞ ) were evaluated by the average bioequivalence (ABE) method ( S WR < 0.294). The geometric mean ratio (GMR) of T/R for C max was 106.49%, while the 95% upper confidence bound was < 0. The GMRs of AUC 0– t and AUC 0–∞ were 103.34% and 101.28%, and the 90% confidence intervals (CIs) of the test/reference were 95.90–111.35%/94.85–108.15%, respectively. In the fed state, the RSABE approach was applied to estimate the bioequivalence of C max ( S WR >0.294), and the ABE approach was applied to estimate the bioequivalence of AUC 0–t and AUC 0– ∞ (S WR < 0.294). The GMR for C max was 99.80%, while the 95% upper confidence bound value was < 0. The GMRs of AU...

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Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment

Sun,

Niu,

Zhang

et al. 2024

AAPS PharmSciTech

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A Bioequivalence Study With Pharmacokinetic Endpoints for Azithromycin Eye Drops

Cited by 3 publications

References 23 publications

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

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

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

Keratin Formed Bioadhesive Ophthalmic Gel for the Bacterial Conjunctivitis Treatment

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