The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against <i>Haemophilus parasuis</i>

Lei, Zhixin; Liu, Qianying; Yang, Bing; Ahmed, Saeed; Cao, Jiyue; He, Qigai

doi:10.18632/oncotarget.23018

Cited by 13 publications

(48 citation statements)

References 63 publications

(91 reference statements)

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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%

“…PK evaluation plays a key role in new animal drugs development. Moreover, it could support a supplemental application for modification of administration routes, dosage forms, scheme, and manufacturing process which may make a significant effect for usage (Lei et al, 2017b , c , 2018 ; Zaid et al, 2017 ). As a newly developed antibiotic substitute, Piscidin 1 has barely been investigated for PK with different administrations and dosages.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…The resistance bacteria were excluded, and the wild-type PM should be defined for microorganisms which did not have any acquired resistance mechanisms to the tildipirosin. Additionally, the ECV calculated as the peak MIC for wild-type PM comprised over 95% in the MIC distributions according to the guidelines of CLSI and the previously described reports ( Turnidge and Paterson, 2007 ; Pfaller et al, 2010 , 2011 ; Lei et al, 2018a ). The wild-type MIC distributions were checked and amended on the basis of standard distribution at the lower end of the MIC range for attaining the suitable distribution of MICs, which was executed with Sigma-Stat software (version 3.5, Systat Software Inc., United States).…”

Section: Methodsmentioning

confidence: 99%

“…According to the MIC of tildipirosin against PM04 in MIC value, TSA plates were made with various concentrations of tildipirosin from the range of 1/4 to 32 MIC detailed in the previous study by Zhang and Lei and their companions ( Zhang et al, 2016 ; Lei et al, 2018a ). From the bacterial fluid, 100 μl was diluted with normal sterile saline (10 -1 to 10 -5 dilution ratio), then aliquots of the last four diluted samples were plunged onto the TSA plates at 0, 2, 4, 6, 8, 10, 12, and 24 h of culture, which were incubated in the atmosphere having CO 2 for 48 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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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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Tildipirosin: An effective antibiotic against Glaesserella parasuis from an in vitro analysis

Peres¹,

Prigol²,

Gutiérrez-Martín

et al. 2020

Veterinary and Animal Science

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

Cited by 13 publications

References 63 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

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

Tildipirosin: An effective antibiotic against Glaesserella parasuis from an in vitro analysis

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