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.
| Reference Key |
zhou2017frontierspharmacodynamic
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| Authors | ;Yu-Feng Zhou;Yu-Feng Zhou;Hui-Min Peng;Hui-Min Peng;Ming-Xiao Bu;Ming-Xiao Bu;Ya-Hong Liu;Ya-Hong Liu;Jian Sun;Jian Sun;Xiao-Ping Liao;Xiao-Ping Liao |
| Journal | chemical research in chinese universities |
| Year | 2017 |
| DOI |
10.3389/fphar.2017.00684
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| URL | |
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