Pharmacokinetic-Pharmacodynamic Profile, Bioavailability, and Withdrawal Time of Tylosin Tartrate Following a Single Intramuscular Administration in Olive Flounder (Paralichthys olivaceus)

Abstract

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.

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

“…Tylosin bioavailability following IM injection in chicken was ranged from 22.5 to 34.0%, while it was ranged from 70 to 95% in pigs, cows, and sheep after oral administration [ 12 – 14 ]. In contrast, the reported oral bioavailability in mink is poor (41%), while the IM-injected bioavailability in olive flounder is high (approximately 87%) [ 7 , 15 ].…”

“…Several recent studies suggested that tylosin-based antibiotics could be a good candidate to treat bacterial infections in fishes [ 1 , 7 ]. The pharmaco-kinetics/dynamics profiles of this drug have been explored to determine the optimal treatment regime in fishes [ 1 , 7 ]. Through a variety of studies on safety and efficacy of tylosin in fish, it was revealed that use of tylosin to fish has lots of advantages, including rapid absorption, low acute toxicity, and no critical adverse effects such as mortality or histopathological changes at appropriate therapeutic doses [ 1 , 7 ].…”

“…The pharmaco-kinetics/dynamics profiles of this drug have been explored to determine the optimal treatment regime in fishes [ 1 , 7 ]. Through a variety of studies on safety and efficacy of tylosin in fish, it was revealed that use of tylosin to fish has lots of advantages, including rapid absorption, low acute toxicity, and no critical adverse effects such as mortality or histopathological changes at appropriate therapeutic doses [ 1 , 7 ]. Therefore, establishment of maximum residue limit for tylosin in fish is required because of its potential use in aquaculture to increase production by avoiding disease outbreaks.…”

Optimizing tylosin dosage for co-infection of Actinobacillus pleuropneumoniae and Pasteurella multocida in pigs using pharmacokinetic/pharmacodynamic modeling

“…This suggests that the current dose of 20 mg/kg may be insufficient for treating wild-type populations. While most studies ( Boothe et al, 2002 ; Avci and Elmas, 2014 ; Lee et al, 2021 ) have primarily focused on the drug concentrations in serum/plasma for PK/PD studies, it is crucial to consider the interstitial tissue as it is commonly invaded by most bacteria. Evaluating the antibiotic concentration in the interstitial fluid of the target tissue becomes essential for assessing the antibacterial effects ( Matzneller et al, 2013 ).…”

Influence of Intramuscular Injection Sites on Pharmacokinetics of Amoxicillin in Olive Flounder (Paralichthys olivaceus) and Its Implication for Antibacterial Efficacy

“…In the aquaculture industry, antibiotics are commonly administered via injection for the olive flounder (Paralichthys olivaceus) owing to the advantages it offers over oral administration in certain circumstances [1,2]. Compared to other farmed fish species, the olive flounder has a calm demeanor and flat body, which makes physical injection of drugs feasible [1].…”