Bromhexine effects on enrofloxacin penetration in bronchial chicken secretion

MESTORINO, NORA; BULDAIN, DANIEL; GORTARI, LIHUEL; BUCHAMER, ANDREA; ALIVERTI, FLORENCIA; MARCHETTI, MARÍA LAURA

Roma

Conferencia; Ninth International Conference on Antimicrobial Agents In Veterinary Medicine (AAVM); 2018

Bromhexine (BROM) is a derivate of the Adhatoda vasica, plant used in some countries for the treatment of various respiratory diseases. It enhances the secretion of various mucus components by modifying its physicochemical characteristics, increasing mucociliary clearance. Furthermore, the co-administration of antibiotics with bromhexine amplified the actions of the antibiotic. Its use is approved intramuscularly or orally in calves, pigs and chickens at a rate of 0.5 mg/kg/day for 5 consecutive days. Our objective was to determine the possible increase of penetration of enrofloxacin (ENR) into bronchial secretions when combined with the fluidifying BROM. One hundred and twenty chickens were divided in two groups of sixty animals each: one group was treated with ENR alone and the other was treated with the ENR/BROM combination. Both formulations were administered at 10 mg/kg for five days. Plasma and bronchial secretions samples were obtained at different times during treatment and up to 24 h post-administration. The presence of ENR and its metabolite ciprofloxacin in all samples were determined by HPLC with fluorescence detection. Pharmacokinetic analysis was performed by non-compartmental methods with Phoenix® WinNonlin® 8.0, copyright ©2005-2017, Certara, L.P. ENR maximum plasma concentration (Cmax) obtained after ENR/BROM combination administration, was higher than the achieved after the administration of ENR only (0.77 μg/mL vs. 0.63 μg/mL, P=0.0332), and was achieved later (Tmax 105.75 h vs 90 h). Although no statistically significant difference was found when comparing the areas under the curve plasma concentration as a function of time (AUC) between both groups, it did obtain significant difference in the medium residence time (MRT 88.14 vs 80.66 h, P=0.0214). In bronchial lavage, greater differences were found after combination administration, a higher Cmax (0.90 vs 0.49 μg/mL, P=0.0344) was obtained more quickly (Tmax of 24 h vs 58.29 h, P=0.0082), with a higher bioavailability (AUC 59.50 vs 36.03 μg.h/mL, P=0.0457), but the MRT was shorter (55.10 vs 81.66 h, P=0.0139). The results showed that BROM facilitates the ENR penetration into the airways, achieving higher concentrations and faster than when given ENR alone, which would allow to quickly reach the predictors of antimicrobial efficacy (AUC/MIC) to attack the microorganisms responsible of respiratory infections in broilers.