COMPARATIVE, RANDOMISED, SINGLE-DOSE, CROSSOVER BIOAVAILABILITY STUDY OF TWO FORMULATIONS OF AZITHROMYCIN 500 mg FILM-COATED TABLETS IN HEALTHY VOLUNTEERS UNDER FASTING CONDITIONS

Gordana Damjanovska; Emilija Atanasovska; Nikola Labacevski

Gordana Damjanovska Medical doctor, PhD, Specialist for preclinical and clinical pharmacology and toxicology, Skopje, North Macedonia
Emilija Atanasovska Institute for preclinical and clinical pharmacology and toxicology, Medical faculty, “Ss.Cyril and Metodius University”in Skopje, North Macedonia
Nikola Labacevski Institute for preclinical and clinical pharmacology and toxicology, Medical faculty, “Ss.Cyril and Metodius University”in Skopje, North Macedonia

Abstract

Abstract

Bioequivalence studies are clinical studies for determining bioavailability of investigated medicinal products and are conducted in accordance with EU Directive 2001/20/ EMA - Note for Guidance on the Investigation of Bioavailability and Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr**), Objective: The objective of this study was to compare the rate and extent of absorption of single dose of 500mg AZITHROMYCIN (as test or reference preparation) in two periods of treatment with 28 days wash out between them, administered to healthy volunteers in a single-dose, randomized, 2 way cross-over study under fasting conditions.

Material and methods: Clinical study included forty-four male healthy volunteers with fulfilled inclusion criteria and signed Informed consent in accordance with the Clinical Study Protocol approved by Ethical Committee for clinical and other investigations related to medicines and medical devices at the Agency for Medicines and Medical Devices of Republic of North Macedonia. Validated HPLC-MS/MS method for AZITHROMYCIN form plasma determination was used, and with pharmacokinetic analysis, pharmacokinetics variables were determined: Primary Variables:Cmax; AUC0-72h Secondary Variables:Tmax; AUC0-.Statistycal analysis:An analysis of variance (ANOVA) was used to evaluate treatment, sequence and period effects. Safety:Descriptive statistics were calculated for demographic data and for adverse events.

Results:Pharmacokinetic:A total of 44 subjects had pharmacokinetic samples, 43 of them were included in the pharmacokinetic statistical analysis Safety:Both treatments (A and B) appear to be safe and well tolerated after single oral dose. No severe adverse events, serious adverse events or deaths

Conclusion:Both products are bioequivalent based on the results of main analysis (equivalence of AUC_0-72hand C_maxusing ln-transformed data).

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