Evaluation of Marbofloxacin in Beagle Dogs After Oral Dosing: Preclinical Safety Evaluation and Comparative Pharmacokinetics of Two Different Tablets

Abstract

The current study evaluates a tested marbofloxacin tablet (MBT) (Petsen), in terms of bioavailability and pharmacokinetics (PK) in a comparison of the commercialized and standard tablet (Marbocyl) in beagle dogs. Four different bacterial species were selected for the determination of the minimal inhibitory concentration (MIC) against marbofloxacin (MBF). Target animal safety studies were conducted with a wide spectrum of dosages of Petsen. Pharmacokinetics and bioavailability of Petsen were observed after the oral administration of a recommended dosage of 2 mg/kg. The MIC90 of MBF against Staphylococcus aureus, Escherichia coli, Pasteurella multocida, and Streptococcus were 2.00, 4.00, 0.25, and 0.50 μg/ml, respectively. These results showed that the MBT has an expected antimicrobial activity in vitro. The main parameters of t1/2β, Clb, AUC0−∞, Cmax, and Ke were 22.14 h, 0.15 L/h, 13.27 μg.h/ml, 0.95 μg/ml, 0.09 h−1, and 16.47 h, 0.14 L/h, 14.10 μg.h/ml, 0.97 μg/ml, 0.11 h−1 after the orally administrated Petsen and Marbocyl, while no biologically significant changes and toxicological significance have been found by their comparison. These findings indicate that the Petsen had a slow elimination, high bioavailability and kinetically similar to the commercialized Marbocyl. Furthermore, no statistically significant differences were distinguished on the continuous gradient dosages of 2, 6, and 10 mg/kg in the term of the clinical presentation. The present study results displayed that the tested MBT (Petsen) was safe, with limited toxicity, which was similar to the commercialized tablet (Marbocyl), could provide an alternative MBT as a veterinary medicine in beagle dogs.

Pharmacological Studies on Marbofloxacin on Diarrheic Calves

“…Our result established with (Zhixin Lei et al, 2018) who recorded increase in WBC count and decrease in platelet in the 6 and 10 mg/kg treatment groups of peagle dog on day 14 and 40 compared to control group.…”

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

“…Based on the killing-time curve profiles of tildipirosin against PM04 ( Figure 3 ) in vitro and ex vivo , it was obvious that tildipirosin presented the concentration-dependent action and the parameter “AUC 24 h /MIC” was generally regarded as the threshold for the successful therapeutic outcome of macrolides ( Lei et al, 2017b , 2018b , c ). In the previously published studies ( Sang et al, 2016 ; Wang et al, 2016 ; Zhang et al, 2016 ; Lei et al, 2017a , 2018a ), the AUC 24 h /MIC > 30 h, and AUC 24 h /MIC > 125 h were used frequently for macrolides and fluoroquinolones against Gram-negative bacteria; these thresholds might be different for different drugs, against different kinds of bacteria due to the differences in the immune status of target animals and pathogens ( Toutain et al, 2002 ; Ahmad et al, 2015 ).…”

“…The Monte Carlo simulation (including 10,000 iterations) was performed using the Crystal Ball software (version 7.2.2, Oracle, United States) based on the selected PK/PD target index (AUC 24 /MIC, E = -3, bactericidal activity) ( Lei et al, 2017a , b , c , 2018b ). The CO PD was calculated as the MIC when PTA reached up to 90% based on the CLSI guidelines and other previously described studies ( Turnidge and Paterson, 2007 ; Lei et al, 2018a ).…”

Uso das fluoroquinolonas em cães e gatos domésticos

“…Entre as infecções tratadas com este medicamento, incluem-se as de pele e tecido mole, ósseas, do trato urinário inferior, as pneumonias e as doenças provocadas por micro-organismos intracelulares, é eficaz no tratamento de infecções hematógenas, como as provocadas por Mycoplasma haemofelis em gatos, neste caso, é indicado a dose de 2,75 mg/kg a cada 24 horas por via oral durante 14 dias. Em cães, a meia-vida da marbofloxacina é de 7-9 horas, mas, em alguns estudos, pode ser maior (Lei, et al, 2018;Papich, 2012).…”

“…Uma vez que outras quinolonas de uso veterinário são preferidas para o tratamento inicial (enrofloxacino, orbifloxacino, danofloxacino e marbofloxacino), a administração de moxifloxacino não é comum. Os resultados da utilização em pequenos animais são esparsos e os esquemas terapêuticos derivam, principalmente, da administração em seres humanos (Ceric, et al, 2019;Lei, et al, 2018;Papich, 2012). (Tabela 1).…”