Abstract
Simple SummaryFishes usually stop eating food when they are sick, and treating diseased fish with oral drugs is a serious hurdle in the aquaculture industry. Tylosin tartrate is a potent bacterial-killing agent useful against frequently occurring bacterial fish infections. We tested the effectiveness against pathogenic bacteria and the human safety of the drug for possible application to cultured olive flounder, one of the most important culture species in far eastern Asian countries. Tylosin tartrate was very effective in killing the pathogenic bacteria grown in artificial culture media, and it was also demonstrated that the drug reached body concentrations in olive flounder, high enough to kill the pathogen. In addition, we also determined how long to wait until the fish clears the injected drug out and it is possible for human consumption. These results will pave a new method for disease treatment useful for olive flounder farming.The objective of this study was to demonstrate the pharmacokinetic–pharmacodynamic profile, bioavailability, and withdrawal time of tylosin tartrate (TT) administered to olive flounder via intramuscular (IM, 10 or 20 mg/kg, n = 240) and intravascular (IV, 10 mg/kg, n = 90) injections. Serum concentrations of tylosin were determined using a validated liquid chromatography-tandem mass spectrometry method. According to the non-compartmental analysis, the bioavailability of TT was 87%. After the IV injection, the terminal half-life, total body clearance, volume of distribution, and mean residence time of TT were 21.07 h, 0.07 L/kg/h, 2.15 L/kg, and 16.39 h, respectively. Rapid absorption (Tmax 0.25 h), prolonged action (terminal half-life, 33.96 and 26.04 h; MRT, 43.66 and 33.09 h), and linear dose–response relationship (AUC0-inf, 123.55 and 246.05 µg/mL*h) were monitored following 10 and 20 mg/kg IM injection. The withdrawal time of TT from muscle (water temperature, 22 °C) was 9.84 days, rounded up to 10 days (220 degree days). Large Cmax/MIC90, AUC0-inf/MIC90, and T > MIC90 values were obtained for Streptococcus isolates and these PK/PD indices satisfied the criteria required for efficacy evaluation. This study lays a foundation for the optimal use of TT and provides valuable information for establishing therapeutic regimens.
Highlights
Antibiotics are typically administered to farmed fish via the oral route
Our study provides meaningful pharmacokinetic results of injectable TT in olive flounder, which, in relation to the absorption of TT, is quite rapid from the IM site, showing a long t1/2λz and MRT is beneficial for efficacy, and a linear dose–response relationship with area under the concentration–time curve (AUC)
Our results demonstrated that large T > MIC90 values and AUC0–inf/MIC90 were obtained for S. iniae and S. parauberis isolates after single IM injection of TT at both 10 and 20 mg/kg to olive flounder (Table 4)
Summary
Antibiotics are typically administered to farmed fish via the oral route. The critical disadvantage of oral administration is the difficulty in administering the drug to a sick fish with a poor appetite [1]. Despite the other main disadvantages, such as high labor costs and tissue damage, one of the solutions to the low amount of drug intake is changing the drug from one that allows for oral administration to injection [2]. Olive flounder (Paralichthys olivaceus) typically remain calm during injection, so it can be treated without causing excessive stress. A few single and complex antibiotics that could be administered via injection, such as ampicillin, amoxicillin, ceftiofur, and the florfenicolamoxicillin combination, have been successfully implemented to treat P. olivaceus in the Korean aquaculture industry [3]. It is broadly used to treat the following conditions: respiratory infection, mastitis, and arthritis in cows; atrophic rhinitis and dysentery in pigs; and mycoplasma infection in birds [4,7,8]
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