Abstract
Clinical evidence indicated that effective substitution of azithromycin capsule with a tablet dosage form should be based on evidence of providing equivalent in vivo AUC/MIC ratio at the site of infection. This study was designed to compare the bioavailability of a generic azithromycin capsule and assess its bioequivalence with Zithromax tablets marketed in Jamaica. Healthy adult volunteers were recruited following official institutional protocols and randomly assigned to pre- and post wash-over periods of the tests. Sampled plasma levels were analyzed using validated HPLC method. Drug’s bio-disposition mechanism in the subjects was determined using the Gastroplus® pharmacokinetics software. Model evaluation with Akaike Information Criterion (AIC) and Schwarz Criterion (SC) indicated one-compartment and two-compartment open models as the best for modeling azithromycin bioavailability from tablets and capsules respectively. However, statistical analysis showed no statistical significance between the respective bioavailability parameters of capsules and tablets, and they fell generally within the US FDA acceptance range of -20% to +25 % of reference product. Azithromycin release from tablets fits one-compartment while from capsules fits the two-compartment open models respectively. Azithromycin capsules were bioequivalent to its proprietary tablets and can be substituted in black male subjects if administered at least two hours before meals.
Highlights
Azithromycin is a15-membered ring, semi-synthetic macrolide antibiotic with two deoxysugars, derived from erythromycin through a methyl-substituted nitrogen atom in the lactone ring
Model dependent evaluation of azithromycin capsule against proprietary tablet shows no statistically significant difference between their bioavailability parameters as they generally fell within the -20 to + 25 % range accepted by the FDA
Since drug absorption and systemic distribution of azithromycin are both firstorder processes, the relative rapidity of drug release from capsule may be responsible for the observed two-compartment behavior compared with tablets which demonstrated slower and polyphasic dissolution profile
Summary
Azithromycin is a15-membered ring, semi-synthetic macrolide antibiotic with two deoxysugars, derived from erythromycin through a methyl-substituted nitrogen atom in the lactone ring. Its chemical name is 9-deoxy-9a-azo-9a-methyl-9ahomoerythromycin A, with molecular weight 748.88 and chemical formula C38H72N 2O12. Azithromycin showed comparative effectiveness as ciprofloxacin clinically and bacteriologically against sensitive and multidrug resistant (MDR) S. typhi in Egypt (Girgis et al, 1999). It was more effective than doxycycline and ciprofloxacin on Chlamydia trachomatis and gonorrhea. It is currently used in the management of patients with cystic fibrosis (Wilms et al, 2012)
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