pharmacodynamic evaluation and pk/pd-based dose prediction of tulathromycin: a potential new indication for streptococcus suis infection

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2017
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Abstract
Tulathromycin is the first member of the triamilide antimicrobial drugs that has been registered in more than 30 countries. The goal of this study is to provide a potential new indication of tulathromycin for Streptococcus suis infections. We investigated the pharmacokinetic and ex vivo pharmacodynamics of tulathromycin against experimental S. suis infection in piglets. Tulathromycin demonstrated a relatively long elimination half-life (74.1 h) and a mean residence time of 97.6 h after a single intramuscular administration. The minimal inhibitory concentration (MIC) and bactericidal concentration in serum were markedly lower than those in broth culture, with Mueller–Hinton broth/serum ratios of 40.3 and 11.4, respectively. The post-antibiotic effects were at 1.27 h (1× MIC) and 2.03 h (4× MIC) and the post-antibiotic sub-MIC effect values ranged from 2.47 to 3.10 h. The ratio of the area under the concentration–time curve divided by the MIC (AUC/MIC) correlated well with the ex vivo antimicrobial effectiveness of tulathromycin (R2 = 0.9711). The calculated AUC12h/MIC ratios in serum required to produce the net bacterial stasis, 1-log10 and 2-log10 killing activities were 9.62, 18.9, and 32.7, respectively. Based on the results of Monte Carlo simulation, a dosage regimen of 3.56 mg/kg tulathromycin was estimated to be effective, achieving for a bacteriostatic activity against S. suis infection over 5 days period. Tulathromycin may become a potential option for the treatment of S. suis infections.
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zhou2017frontierspharmacodynamic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yu-Feng Zhou, Hui-Min Peng, Ming-Xiao Bu, Ya-Hong Liu, Jian Sun, Xiao-Ping Liao
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Journal chemical research in chinese universities
Year 2017
DOI
10.3389/fphar.2017.00684
URL
http://journal.frontiersin.org/article/10.3389/fphar.2017.00684/full
Keywords
streptococcus suis pharmacology

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