Bioavailability and pharmacokinetic comparison between generic and branded azithromycin capsule: a randomized, double-blind, 2-way crossover in healthy male Thai volunteers.

BACKGROUND

Azithromycin is a semisynthetic azalide antibiotic with extensive tissue penetration and a prolonged t(12). It is used once daily for 3 days in the treatment of a number of bacterial infections. However, based on a literature search, information concerning its pharmacokinetic properties, including the relative bioavailability of a newly developed generic capsule formulation compared with an established branded one in the Thai population, has not been reported.

OBJECTIVE

The aim of this study was to compare the relative bioavailability and other pharmacokinetic properties of a newly developed generic capsule formulation of azithromycin with those of an established branded formulation in healthy male volunteers in Thailand.

METHODS

A randomized, double-blind, 2-way crossover study was performed in healthy male Thai volunteers under fasting conditions with a washout of 30 days between the study periods. A single dose of 2 x 250-mg azithromycin capsules was orally administered, and blood samples were collected over a period of 120 hours. Plasma azithromycin concentrations were determined using a validated high-performance liquid chromatography method with fluorescence detection after derivatization with 9-fluorenylmethyloxycarbonyl chloride. A plasma concentration-time curve was generated for each volunteer from which the C(max), T(max), AUC(0-Iast), AUC(0-infinity), t(1/2), and kappa(e) were determined using noncompartmental analysis. Bioequivalence was defined using regulatory requirements set forth by Thailand, Association of Southeast Asian Nations, and the US Food and Drug Administration (bioequivalence acceptance range, 0.80-1.25).

RESULTS

A total of 14 volunteers completed the study. The mean age of volunteers was 20.8 years (range, 19-23 years), and the mean body weight was 62.8 kg (range, 50.6-70.0 kg). The mean (SD) T(max), C(max), AUC(0-last), and AUC(0-infinity) values after administration of the generic and branded formulations were 1.46 (0.41) versus 1.54 (0.41) hours, 425.23 (208.45) versus 431.75 (198.16) ng/mL, 3919.77 (1549.65) versus 4344.79 (1654.98) ng . h/mL, and 4027.05 (1839.13) versus 4515.53 (2203.87) ng . h/mL, respectively. The relative bioavailability of the generic and branded formulations were 1.00 (0.17). The mean (SD) t1/2 values after administration of the generic and branded formulations were 26.43 (10.92) and 28.10 (13.13) hours, respectively. The analysis of variance results of the natural logarithm (In) -transformed values found no significant effect of formulation, period, or sequence on the studied pharmacokinetic parameters. The 90% CIs of the treatment ratios for the Intransformed values of C(max), AUC(0-last), and AUC(0-infinity) were 0.82 to 1.11, 0.91 to 1.06, and 0.91 to 1.08, respectively. All were within the standard bioequivalence acceptance range of 0.80 to 1.25. No adverse events were reported in this study.

CONCLUSIONS

In this small study in a selected population of healthy male Thai volunteers, the C(max) and AUC were not statistically significantly different between generic and branded formulations of a single, 2 x 250-mg dose of azithromycin capsules. The generic and branded formulations were found to be bioequivalent. Both formulations were well tolerated.