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Integrated pharmacokinetics/pharmacodynamics parameters-based dosing guidelines of enrofloxacin in grass carp Ctenopharyngodon idella to minimize selection of drug resistance.

Xu L, Wang H, Yang X, Lu L - BMC Vet. Res. (2013)

Bottom Line: The pathogenic A. hydrophila strain (AH10) in grass carp was identified and found to be sensitive to enrofloxacin.Dosing of 30 μg/g resulted in serum maximum concentration (Cmax) of 7.151 μg/mL, and concentration in serum was above MPC till 24 h post the single dose.Based on integrated PK/PD parameters (AUC/MIC, Cmax/MIC, and T>MPC), the results of this study established a principle, for the first time, on drawing accurate dosing guideline for pharmacotherapy against A. hydrophila strain (AH10) for prevention of drug-resistant mutants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Freshwater Fishery Germplasm Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, People's Republic of China.

ABSTRACT

Background: Antibiotic resistance has become a serious global problem and is steadily increasing worldwide in almost every bacterial species treated with antibiotics. In aquaculture, the therapeutic options for the treatment of A. hydrophila infection were only limited to several antibiotics, which contributed for the fast-speed emergence of drug tolerance. Accordingly, the aim of this study was to establish a medication regimen to prevent drug resistant bacteria. To determine a rational therapeutic guideline, integrated pharmacodynamics and pharmacokinetics parameters were based to predict dose and dosage interval of enrofloxacin in grass carp Ctenopharyngodon idella infected by a field-isolated A. hydrophila strain.

Results: The pathogenic A. hydrophila strain (AH10) in grass carp was identified and found to be sensitive to enrofloxacin. The mutant selection window (MSW) of enrofloxacin on isolate AH10 was determined to be 0.5-3 μg/mL based on the mutant prevention concentration (MPC) and minimum inhibitory concentration (MIC) value. By using high-performance liquid chromatography (HPLC) system, the Pharmacokinetic (PK) parameters of enrofloxacin and its metabolite ciprofloxacin in grass carp were monitored after a single oral gavage of 10, 20, 30 μg enrofloxacin per g body weight. Dosing of 30 μg/g resulted in serum maximum concentration (Cmax) of 7.151 μg/mL, and concentration in serum was above MPC till 24 h post the single dose. Once-daily dosing of 30 μg/g was determined to be the rational choice for controlling AH10 infection and preventing mutant selection in grass carp. Data of mean residue time (MRT) and body clearance (CLz) indicated that both enrofloxacin and its metabolite ciprofloxacin present similar eliminating rate and pattern in serum, muscle and liver. A withdraw time of more than 32 d was suggested based on the drug eliminating rate and pharmacokinetic model described by a polyexponential equation.

Conclusions: Based on integrated PK/PD parameters (AUC/MIC, Cmax/MIC, and T>MPC), the results of this study established a principle, for the first time, on drawing accurate dosing guideline for pharmacotherapy against A. hydrophila strain (AH10) for prevention of drug-resistant mutants. Our approach in combining PK data with PD parameters (including MPC and MSW) was the new effort in aquaculture to face the challenge of drug resistance by drawing a specific dosage guideline of antibiotics.

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Ciprofloxacin concentration-time curves in serum and tissues of grass carp at different administration doses of enrofloxacin. Standard deviation is given at vertical bars. (n = 5, The mean ± SD). At three doses of enrofloxacin, the Cmax of ciprofloxacin in liver is highest and the Cmax of ciprofloxacin in serum is lowest. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. (A: Serum; B: Liver; C: Muscle D: Kidney).
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Figure 3: Ciprofloxacin concentration-time curves in serum and tissues of grass carp at different administration doses of enrofloxacin. Standard deviation is given at vertical bars. (n = 5, The mean ± SD). At three doses of enrofloxacin, the Cmax of ciprofloxacin in liver is highest and the Cmax of ciprofloxacin in serum is lowest. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. (A: Serum; B: Liver; C: Muscle D: Kidney).

Mentions: Figure 3 depicted the time course of metabolite ciprofloxacin concentrations in serum, liver, kidney, and muscle from grass carp after oral gavage of enrofloxacin at a dose of 10 μg/g, 20 μg/g, and 30 μg/g, respectively. In general, ciprofloxacin was detectable 0.5 h after drug delivery and high dose resulted a shorter time to reach Cmax. As expected, only a small portion of enrofloxacin was transmitted to ciprofloxacin. At the dose of 30 μg/g of enrofloxacin, the Cmax of ciprofloxacin in serum, liver, muscle, and kidney was only 0.254 μg/mL, 1.480 μg/g, 0.329 μg/g, and 0.386 μg/g, respectively. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. For example, the Tmax for serum, liver, kidney, and muscle at the dose of 30 μg/g was 0.5 h, 0.5 h, 1 h and 4 h, respectively.


Integrated pharmacokinetics/pharmacodynamics parameters-based dosing guidelines of enrofloxacin in grass carp Ctenopharyngodon idella to minimize selection of drug resistance.

Xu L, Wang H, Yang X, Lu L - BMC Vet. Res. (2013)

Ciprofloxacin concentration-time curves in serum and tissues of grass carp at different administration doses of enrofloxacin. Standard deviation is given at vertical bars. (n = 5, The mean ± SD). At three doses of enrofloxacin, the Cmax of ciprofloxacin in liver is highest and the Cmax of ciprofloxacin in serum is lowest. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. (A: Serum; B: Liver; C: Muscle D: Kidney).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3717066&req=5

Figure 3: Ciprofloxacin concentration-time curves in serum and tissues of grass carp at different administration doses of enrofloxacin. Standard deviation is given at vertical bars. (n = 5, The mean ± SD). At three doses of enrofloxacin, the Cmax of ciprofloxacin in liver is highest and the Cmax of ciprofloxacin in serum is lowest. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. (A: Serum; B: Liver; C: Muscle D: Kidney).
Mentions: Figure 3 depicted the time course of metabolite ciprofloxacin concentrations in serum, liver, kidney, and muscle from grass carp after oral gavage of enrofloxacin at a dose of 10 μg/g, 20 μg/g, and 30 μg/g, respectively. In general, ciprofloxacin was detectable 0.5 h after drug delivery and high dose resulted a shorter time to reach Cmax. As expected, only a small portion of enrofloxacin was transmitted to ciprofloxacin. At the dose of 30 μg/g of enrofloxacin, the Cmax of ciprofloxacin in serum, liver, muscle, and kidney was only 0.254 μg/mL, 1.480 μg/g, 0.329 μg/g, and 0.386 μg/g, respectively. Similar to enrofloxacin, the time to Cmax in muscle for ciprofloxacin was significantly longer than in serum and other tissues. For example, the Tmax for serum, liver, kidney, and muscle at the dose of 30 μg/g was 0.5 h, 0.5 h, 1 h and 4 h, respectively.

Bottom Line: The pathogenic A. hydrophila strain (AH10) in grass carp was identified and found to be sensitive to enrofloxacin.Dosing of 30 μg/g resulted in serum maximum concentration (Cmax) of 7.151 μg/mL, and concentration in serum was above MPC till 24 h post the single dose.Based on integrated PK/PD parameters (AUC/MIC, Cmax/MIC, and T>MPC), the results of this study established a principle, for the first time, on drawing accurate dosing guideline for pharmacotherapy against A. hydrophila strain (AH10) for prevention of drug-resistant mutants.

View Article: PubMed Central - HTML - PubMed

Affiliation: Key Laboratory of Freshwater Fishery Germplasm Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, People's Republic of China.

ABSTRACT

Background: Antibiotic resistance has become a serious global problem and is steadily increasing worldwide in almost every bacterial species treated with antibiotics. In aquaculture, the therapeutic options for the treatment of A. hydrophila infection were only limited to several antibiotics, which contributed for the fast-speed emergence of drug tolerance. Accordingly, the aim of this study was to establish a medication regimen to prevent drug resistant bacteria. To determine a rational therapeutic guideline, integrated pharmacodynamics and pharmacokinetics parameters were based to predict dose and dosage interval of enrofloxacin in grass carp Ctenopharyngodon idella infected by a field-isolated A. hydrophila strain.

Results: The pathogenic A. hydrophila strain (AH10) in grass carp was identified and found to be sensitive to enrofloxacin. The mutant selection window (MSW) of enrofloxacin on isolate AH10 was determined to be 0.5-3 μg/mL based on the mutant prevention concentration (MPC) and minimum inhibitory concentration (MIC) value. By using high-performance liquid chromatography (HPLC) system, the Pharmacokinetic (PK) parameters of enrofloxacin and its metabolite ciprofloxacin in grass carp were monitored after a single oral gavage of 10, 20, 30 μg enrofloxacin per g body weight. Dosing of 30 μg/g resulted in serum maximum concentration (Cmax) of 7.151 μg/mL, and concentration in serum was above MPC till 24 h post the single dose. Once-daily dosing of 30 μg/g was determined to be the rational choice for controlling AH10 infection and preventing mutant selection in grass carp. Data of mean residue time (MRT) and body clearance (CLz) indicated that both enrofloxacin and its metabolite ciprofloxacin present similar eliminating rate and pattern in serum, muscle and liver. A withdraw time of more than 32 d was suggested based on the drug eliminating rate and pharmacokinetic model described by a polyexponential equation.

Conclusions: Based on integrated PK/PD parameters (AUC/MIC, Cmax/MIC, and T>MPC), the results of this study established a principle, for the first time, on drawing accurate dosing guideline for pharmacotherapy against A. hydrophila strain (AH10) for prevention of drug-resistant mutants. Our approach in combining PK data with PD parameters (including MPC and MSW) was the new effort in aquaculture to face the challenge of drug resistance by drawing a specific dosage guideline of antibiotics.

Show MeSH
Related in: MedlinePlus