Comparative plasma exposure and lung distribution of two human use commercial azithromycin formulations assessed in murine model: a preclinical study.
Azithromycin (AZM) therapeutic failure and relapses of patients treated with generic formulations have been observed in clinical practice. The main goal of this research was to compare in a preclinical study the serum exposure and lung tissue concentration of two commercial formulations AZM-based in murine model. The current study involved 264 healthy Balb-C. Mice were divided into two groups (n = 44): animals of Group A (reference formulation -R-) were orally treated with AZM suspension at 10 mg/kg of b.w. Experimental animals of Group B (generic formulation -G-) received identical treatment than Group A with a generic formulation AZM-based. The study was repeated twice as Phase II and III. Serum and lung tissue samples were taken 24 h post treatment. Validated microbiological assay was used to determine the serum pharmacokinetic and lung distribution of AZM. After the pharmacokinetic analysis was observed, a similar serum exposure for both formulations of AZM assayed. In contrast, statistical differences (P < 0.001) were obtained after comparing the concentrations of both formulations in lung tissue, being the values obtained for AUC and Cmax (AZM-R-) +1586 and 122%, respectively, than those obtained for AZM-G- in lung. These differences may indicate large differences on the distribution process of both formulations, which may explain the lack of efficacy/therapeutic failure observed on clinical practice.
Laboratory of Pharmacology, Faculty of Veterinary Medicine, Universidad Nacional del Centro de la Provincia de Buenos Aires, Paraje Arroyo Seco s/n., 7000 Tandil, Argentina ; Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Argentina ; Tandil Veterinary Research Center (CIVETAN-CONICET), Argentina.
Virginia
V
Rivulgo
Mónica
M
Sparo
Mónica
M
Ceci
Elida
E
Fumuso
Alejandra
A
Confalonieri
Gastón
G
Delpech
Sergio F Sánchez
SF
Bruni
D000818:Animals; D017963:Azithromycin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D014018:Tissue Distribution / Q000187:drug effects
D017963:Azithromycin