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  • Küçük Resim
    Öğe
    Pharmacokinetic behaviour and pharmacokinetic-pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations
    (Wiley, 2024) Altan, Feray; Corum, Orhan; Corum, Duygu Durna; Uney, Kamil; Terzi, Ertugrul; Bilen, Soner; Sonmez, Adem Yavuz
    Objective: Doxycycline (DO) has been used in fish for a long time, but there are some factors that have not yet been clarified regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties. Therefore, the aim of this study was to investigate the PK and PK/PD targets of DO after 20 mg/kg intravascular (IV), intramuscular (IM) and oral (OR) gavage administration in rainbow trout (Oncorhynchus mykiss). Methods: Plasma samples were collected at specific time points and subsequently analysed by HPLC-ultraviolet. The PK/PD indices were calculated based on the MIC90 (Aeromonas hydrophila and Aeromonas sobria) values obtained for the respective bacteria and the PK parameters obtained for DO following both IM and OR administration. Results: After IV administration, the elimination half-life (t(1/2 lambda z)), area under the concentration vs. time curve (AUC), apparent volume of distribution at steady-state and total body clearance of DO were 34.81 h, 723.82 h mu g/mL, 1.24 L/kg and 0.03 L/kg/h, respectively. The t(1/2 lambda z) of the DO was found to be 37.39 and 39.78 h after IM, and OR administration, respectively. The bioavailability was calculated 57.02% and 32.29%, respectively, after IM and OR administration. The MIC90 of DO against A. hydrophila and A. sobria was 4 mu g/mL. The PK/PD integration showed that DO (20 mg/kg dose) for A. hydrophila and A. sobria with MIC90 <= 4 mu g/mL achieved target AUC/MIC value after IM administration. Conclusions: These results suggest that when rainbow trout was treated with 20 mg/kg IV and IM administered DO, therapeutically effective concentrations were reached in the control of infections caused by A. hydrophila and A. sobria.
  • Küçük Resim
    Öğe
    Pharmacokinetics, Tissue Residues, and Withdrawal Times of Oxytetracycline in Rainbow Trout (Oncorhynchus mykiss) after Single- and Multiple-Dose Oral Administration
    (Mdpi, 2023) Corum, Orhan; Durna Corum, Duygu; Terzi, Ertugrul; Uney, Kamil
    Simple Summary: Determination of the pharmacokinetics of oxytetracycline (OTC) at single and multiple oral doses revealed its long half-life, very low bioavailability, and strong accumulation in rainbow trout. The withdrawal time (WT) for the safe consumption of rainbow trout muscle+skin varied according to the guidelines set by regulatory authorities in different countries. This study improves the establishment of the optimal dosing regimen following OTC multiple administration and the determination of the appropriate WT for the safety of rainbow trout consumption. The aim of this study was to compare the pharmacokinetics of oxytetracycline (OTC) following single- (60 mg/kg) and multiple-dose oral administrations (60 mg/kg, every 24 h for 7 days) in rainbow trout. It also aimed to determine bioavailability after a single dose and tissue residues and withdrawal times after multiple doses. This study was carried out on 420 rainbow trout at 9 +/- 0.8 degrees C. This study was carried out in two stages: single-dose (intravascular and oral) and multiple-dose treatment. The OTC concentrations in plasma and tissues were measured by high-performance liquid chromatography and analyzed by a non-compartmental method. The withdrawal time (WT) was estimated using the WT 1.4 software. OTC exhibited a long terminal elimination half-life (t(1/2 lambda z)) after IV and oral administration. The oral bioavailability of OTC was very low (2.80%). In multiple-dose treatment, tt(1/2 lambda z), the area under the plasma concentrationtime curve and peak plasma concentration increased significantly after the last day compared to the first day. OTC showed strong accumulation after multiple doses with a value of 5.33. OTC concentrations were obtained in the order liver > kidney > muscle+skin > plasma. At 9 +/- 0.8 degrees C, the WT calculated for muscle+skin was 56 days for Europe and 50 days for China, respectively. The t(1/2 lambda z) (68.94 h) and time (68 h) above the 1 mu g/mL MIC following a single OTC dose may support the extension of the 24 h dosing interval following multiple dosing. However, further studies are required to determine the optimal dosage regimen in multiple-dose OTC treatment in the treatment of infections caused by susceptible pathogens.