PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Lei, Zhixin; Liu, Qianying; Yang, Bing; Khaliq, Haseeb; Cao, Jiyue; He, Qigai

doi:10.3389/fphar.2017.00856

Cited by 10 publications

(15 citation statements)

References 68 publications

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“…Since the difficulty in measuring the antibiotic concentrations at the infected site, the PK data were mostly determined from the serum of the animals in the most previous reports. However, the drug concentrations in plasma are significantly different to target sites which have been reported in the previously published reports such as the marbofloxacin and cyadox concentrations in ileum and plasma (Lei et al, 2017a , b , d , 2018 ; Yan et al, 2017 ). Thus, as a kind of intestinal tract infection virus, it is essential to investigate the PK profiles with an appropriate route in ileum content for Piscidin 1 against PEDV.…”

Section: Introductionmentioning

confidence: 76%

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

et al. 2018

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Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID50), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 μg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in plasma were not applicable value, 25.9 μg*h/ml, 0.041 h−1, 16.97 h, not available value, 22.77 h, 0.067 L/h*kg after i.v administration, 2.37 μg/ml, 18.95 μg*h/ml, 0.029 h−1, 23.50 h, 0.33 h, 30.12 h, 0.095 L/h*kg after i.m administration and 0.73 μg/ml, 9.63 μg*h/ml, 0.036 h−1, 19.46 h, 0.50 h, 26.76 h, 0.171 L/h*kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in ileum content were 1.67 μg/ml, 78.40 μg*h/ml, 0.034 h−1, 20.16 h, 8.12 h, 36.45 h, 0.026 L/h*kg. The Cmax values in plasma (2.37 μg/ml) and ileum content (1.67 μg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study.

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Section: Introductionmentioning

confidence: 76%

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

et al. 2018

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“…In addition, T 1/2 (170.91 h) in this study was higher than that (106 h) reported by Rose. These differences may be explained by the abrasion of epithelial cells, as tildipirosin in lung tissue is passed into the BF during BF collection at postmortem with mechanical separation, leading to substantially higher concentrations and overestimation of the BF concentrations and longer elimination half-life [ 9 , 41 ]. The higher elimination half-life was also caused by the lyses of cells (including high drug concentrations) during the broncho-alveolar lavage procedure.…”

Section: Discussionmentioning

confidence: 99%

“…The urea dilution method was used to estimate the volume of PELF in the BAL fluid, as previously described method [ 17 , 41 – 43 ]. The concentration of urea in plasma and BAL were determined by the urea glutamate dehydrogenase enzymatic method, measured using an automatic dry-type biochemical analyser (DRI-CHEM NX500iVC, FUJIFILM (China) Investment Co., Ltd.) at the National Reference Laboratory of Veterinary Drug Residues (Wuhan, China).…”

Section: Methodsmentioning

confidence: 99%

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

et al. 2017

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The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research.

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“…The susceptibility breakpoint for FF against E. coli has not been provided at present. Therefore, it should be essential to establish such a criterion to monitor the development of resistance (Lei, Liu, Yang, Ahmed, et al., ; Lei, Liu, Yang, Cao, & Qiu, ; Lei et al., 2017a; Lei et al., 2017b; Lei, Liu, Yang, Xiong, et al., ; Lei, Liu, Qi, et al., ; Lei, Liu, Yang, Ahmed, et al., ; Lei, Liu, Yang, Yang, et al., ; Lei, Liu, Zhu, et al., ). Furthermore, it would be better to set the susceptibility of target bacteria to the antibiotics in order to reduce the development of bacterial resistance and strengthen the management of antibiotic use.…”

Section: Introductionmentioning

confidence: 99%

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Lei

Liu

Khaliq

et al. 2019

Vet Pharm & Therapeutics

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Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr, AUC0–∞, Tmax, T1/2, Cmax, CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr−1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr−1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.

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PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

Cited by 10 publications

References 68 publications

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

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