Bioavailability of two oral formulations of azithromycin 500 mg: a randomized, open-label, two-period crossover comparison in healthy Mexican adult subjects.
BACKGROUND
Azithromycin is related to erythromycin but is more active against gram-negative bacteria and less active against streptococci and staphylococci compared with erythromycin. For these reasons, and because of convenience of dosing (QD for 3 days), azithromycin is widely used in Mexico. Although several generic formulations of azithromycin are available in Mexico, information concerning the bioavailability of each formulation in the Mexican population is not available.


OBJECTIVE
The aim of this study was to compare the bioavailability and tolerability of 2 oral formulations of azithromycin 500 mg used in Mexico: Macrozit (trademark of Laboratorios Liomont, S.A. de C.V., Mexico City, Mexico; test formulation) and Azitrocin (trademark of Pfizer, S.A. de C.V., Mexico City, Mexico; reference formulation).


METHODS
This 2 x 2, crossover, randomized, open-label study was conducted at the Department of Pharmacology and Toxicology, Universidad Autóma de Nuevo Leon, Monterrey, Mexico. Eligible subjects were healthy volunteers of either sex and with the following characteristics: age > or =19 to 25 years, weight 54 to 77 kg, and height 159 to 177 cm. Subjects were randomly assigned to receive Macrozit followed by Azitrocin, or vice versa, with a 3-week washout period between doses. After a 12-hour (overnight) fast, subjects received a single, 500-mg dose of each formulation. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity), blood samples were drawn at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 24, 48, 72, 96, and 120 hours after dosing. The formulations were considered bioequivalent if the logarithm (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125% and if P < or = 0.05 for the 90% CIs. Tolerability was assessed by monitoring and subject interview regarding the potential presence of adverse events (AEs).


RESULTS
Twenty-eight subjects were enrolled in the study; 27 completed it (14 men, 13 women; mean age, 21.7 years). Fourteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding ratios of C(max), AUC(0-t), and AUC(0-infinity) were 80.67 to 107.21, 91.39 to 107.59, and 90.61 to 106.19 (all, P < 0.05). Similar results were found for data without a logarithmic transformation. No AEs were found throughout the study.


CONCLUSIONS
In this small study in healthy Mexican volunteers, a single, 500-mg dose of Macrozit was found to be bioequivalent to that of Azitrocin based on the rate and extent of absorption. Both formulations were well tolerated.
Piñeyro-López
Alfredo
A
Department of Pharmacology and Toxicology Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Pineyro-Garza
Everardo
E
Torres-Alanís
Oscar
O
Reyes-Araiza
Raúl
R
Gómez Silva
Magdalena
M
Wacksman
Noemí
N
Rangel
Rubén Luján
RL
de Lago
Alberto
A
González-de la Parra
Mario
M
Namur
Salvador
S
D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D013810:Therapeutic Equivalency
D000900:Anti-Bacterial Agents; D017963:Azithromycin