Comparative plasma exposure and lung distribution of two human-use commercial azithromycin formulations assessed in murine model: a pre-clinical study.

RIVULGO M; SPARO M; CECI, M; DELPECH G.; FUMUSO E; SANCHEZ BRUNI S.

Biomed Research International

Hindawi

Lugar: New Yorkh; Año: 2013 p. 1 - 5

2314-6141

Azithromycin (AZM) therapeutic failure and relapses of patients treated with generic formulations have been observed in clinicalpractice. The main goal of this research was to compare in a preclinical study the serum exposure and lung tissue concentrationof two commercial formulations AZM-based in murine model. The current study involved 264 healthy Balb-C.Mice were dividedinto two groups (𝑛 = 44): animals of Group A (reference formulation -R-) were orally treated with AZM suspension at 10mg/kgof b.w. Experimental animals of Group B (generic formulation -G-) received identical treatment than Group A with a genericformulation AZM-based. The study was repeated twice as Phase II and III. Serum and lung tissue samples were taken 24 h posttreatment. Validated microbiological assay was used to determine the serum pharmacokinetic and lung distribution of AZM. Afterthe pharmacokinetic analysis was observed, a similar serumexposure for both formulations of AZM assayed. In contrast, statisticaldifferences (𝑃 < 0.001) were obtained after comparing the concentrations of both formulations in lung tissue, being the valuesobtained for AUC and Cmax (AZM-R-) +1586 and 122%, respectively, than those obtained for AZM-G- in lung. These differencesmay indicate large differences on the distribution process of both formulations, which may explain the lack of efficacy/therapeuticfailure observed on clinical practice.