Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens <i>Actinobacillus pleuropneumoniae</i> and <i>Pasteurella multocida</i>

Dorey, L.; Pelligand, Ludovic; Cheng, Zhangrui; Lees, P.

doi:10.1111/jvp.12385

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…Our results, when hard water is used to administer the antibiotic, are in agreement with the work of Nielsen and Gyrd-Hansen (1996) who studied OTC F% in fasted and fed piglets and found no statistically significant differences, being 3 ± 1% in both cases, but the authors do not describe characteristics of the water used in the study. Together with low bioavailability in our study, Cmax in all treatment groups fell below MIC90 of OTC reported for most important swine pathogens; namely 1 μg/ml for H.parasuis, 2 μg/ml for A. pleuropneumoniae, 16 μg/ml for P. multocida and 64 μg/ml for B. bronchiseptica and S. suis (Dorey, Pelligand, Cheng, & Lees, 2017;de Jong et al, 2014). C max values were higher in fasted than in fed state for both water qualities; however, these results were similar to those of Nielsen and Gyrd-Hansen (1996) where C max was 0.7 ± 0.3 μg/ml in fasting and 0.4 ± 0.1 μg/ml without fasting.…”

Section: Otc Bioavailability Was Low In All Treatment Groups With Highcontrasting

confidence: 73%

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

Decundo

Dieguez

Martínez

et al. 2019

Veterinary Medicine & Sci

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Water hardness is a critical factor that affects oxytetracycline dissolution by chelation with cations. These interactions may lead to impaired dosing and consequently decrease absorption. Moreover, feed present in gastrointestinal tract may interact with antibiotic and alter pharmacokinetic parameters. In the present study, dissolution profiles of an oxytetracycline veterinary formulation were assessed in purified, soft and hard water. Furthermore, oxytetracycline absolute bioavailability, after oral administration of the drug dissolved in soft or hard water, was evaluated in fed and fasted piglets. A maximum dissolution of 86% and 80% was obtained in soft and hard water, respectively, while in purified water dissolution was complete. Results from in vivo study reconfirmed oxytetracycline's very low oral bioavailability. The greatest values were attained when antibiotic was dissolved in soft water and in fasted animals. Statistically significant lower absolute bioavailability was achieved when hard water was used and/or animals were fed. Moreover, Cmax attained in all treatments was lower than MIC90 of most important swine pathogens. For these reasons, the oral use of OTC formulations, that have demonstrated low oral bioavailability, should be avoided to treat systemic diseases in pigs.

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Section: Otc Bioavailability Was Low In All Treatment Groups With Highcontrasting

confidence: 73%

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

Decundo

Dieguez

Martínez

et al. 2019

Veterinary Medicine & Sci

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“…Based on the ex vivo PK/PD modeling using inhibitory sigmoidal E max model, a favorable correlation ( R 2 = 0.988) was shown between the PK/PD index (AUC 24 h /MIC) and predicted antibacterial efficacy which could be observed in Figure 5 . Furthermore, the predicted population daily dosages over 24 h for tildipirosin against PM acting bacteriostatic, bactericidal, and eradication activities were calculated as 6.10, 9.41, and 10.96 mg/kg for 50% TAR, and 7.86, 12.17 and 14.57 mg/kg TAR, respectively ( Figure 6 and Table 6 ) according to the Monte Carlo simulation which is an effective method to adjust the dosage regimen for clinical use ( Nielsen and Friberg, 2013 ; Dorey et al, 2017 ). Therefore, it was suggested that 12.17 mg/kg could guarantee the clinical efficacy and bactericidal action in this study.…”

Section: Discussionmentioning

confidence: 99%

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

Lei

Liu

et al. 2018

Front. Pharmacol.

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Pasteurella multocida (PM) can invade the upper respiratory tract of the body and cause death and high morbidity. Tildipirosin, a new 16-membered-ring macrolide antimicrobial, has been recommended for the treatment of respiratory diseases. The objective of this research was to improve the dose regimes of tildipirosin to PM for reducing the macrolides resistance development with the pharmacokinetic/pharmacodynamic (PK/PD) modeling approach and to establish an alternate cutoff for tildipirosin against PM. A single dose (4 mg/kg body weight) of tildipirosin was administered via intramuscular (i.m.) and intravenous (i.v.) injection to the pigs. The minimum inhibitory concentration (MIC) values of clinical isolates (112) were measured in the range of 0.0625–32 μg/ml, and the MIC50 and MIC90 values were 0.5 and 2 μg/ml, respectively. The MIC of the selected PM04 was 2 and 0.5 μg/ml in the tryptic soy broth (TSB) and serum, respectively. The main pharmacokinetic (PK) parameters including the area under the curve at 24 h (AUC24 h), AUC, terminal half-life (T1/2), the time to peak concentration (Tmax), peak concentration (Cmax), relative total systemic clearance (CLb), and the last mean residence time (MRTlast) were calculated to be 7.10, 7.94 μg∗h/ml, 24.02, NA h, NA μg/ml, 0.46 L/h∗kg, 8.06 h and 3.94, 6.79 μg∗h/ml, 44.04, 0.25 h, 0.98 μg/ml, 0.43 L/h∗kg, 22.85 h after i.v. and i.m. induction, respectively. Moreover, the bioavailability of i.m. route was 85.5%, and the unbinding of tildipirosin to serum protein was 78%. The parameters AUC24 h/MIC in serum for bacteriostatic, bactericidal, and elimination activities were calculated as 18.91, 29.13, and 34.03 h based on the inhibitory sigmoid Emax modeling. According to the Monte Carlo simulation, the optimum doses for bacteriostatic, bactericidal, and elimination activities were 6.10, 9.41, and 10.96 mg/kg for 50% target and 7.86, 12.17, and 14.57 mg/kg for 90% target, respectively. The epidemiological cutoff value (ECV) was calculated to be 4 μg/ml which could cover 95% wild-type clinical isolates distribution. The PK-PD cutoff (COPD) was analyzed to be 0.25 μg/ml in vitro for tildipirosin against PM based on the Monte Carlo simulation. Compared with these two cutoff values, the finial susceptible breakpoint was defined as 4 μg/ml. The data presented now provides the optimal regimens (12.17 mg/kg) and susceptible breakpoint (4 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.

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“…Furthermore, based on its low toxicity, high bioavailability (near to 100%), and the therapeutic effect equal to or better than other chloramphenicol analogs, FF is recommended to treat for intestinal tract and respiratory infectious diseases in livestock (Kim et al., ; Liu, Fung, Chen, Zeng, & Zhang, ; Ueda, Ohtsuki, & Narukawa, ). There are several previously published reports on the pharmacokinetics (PK) and pharmacodynamics (PD) of FF in the serum in vitro in the chicken, pigs, dogs, and so on (Burch & Klein, ; Dorey, Pelligand, Cheng, & Lees, ; Haritova & Fink‐Gremmels, ; Koc et al., ; Lei, Liu, Qi, et al., ; Lei, Liu, Yang, Ahmed, et al., ; Lei, Liu, Yang, Yang, et al., ; Lei, Liu, Zhu, et al., ; Maaland, Mo, Schwarz, & Guardabassi, ; Poźniak et al., ; Sidhu, Illambas, Potter, Rycroft, & Lees, ; Wang et al., ). However, it is insufficient to assay the practical effect and predict the dosage accordingly with serum and in vitro PK‐PD data.…”

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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Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida

Cited by 16 publications

References 35 publications

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

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

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