Browsing by Author "Uney, K."

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Effect of body size on the oral pharmacokinetics of oxytetracycline in rainbow trout (Oncorhynchus mykiss)
(2024.01.01) Corum, O.; Turk, E.; Corum, D.D.; Terzi, E.; Cellat, M.; Yildirim, O.; Uney, K.
Objective. The aim of this study was to determine the plasma pharmacokinetics of oxytetracycline (OTC) in rainbow trout (Oncorhynchus mykiss) of different body sizes. Methods. The research was carried out on three groups as small (30-50 g), medium (90-110 g) and large (185-215 g) body sizes at 8 +/- 0.5 degree celsius. OTC was administered orally at a dose of 60 mg/kg to all groups. Blood samples were taken at 19 different sampling times until the 384 h after oxytetracycline administration. The plasma concentrations of OTC were measured using high pressure liquid chromatography-ultraviolet and pharmacokinetic parameters were evaluated using non-compartmental analysis. Results. OTC was detected in small-body sized fish until the 336 h and in medium and large-body sized fish until the 384 h. The elimination half-life of OTC was 85.46, 87.24 and 86.98 h in the small, medium and large body size groups, respectively. The peak plasma concentration increased from 0.66 to 1.11 mu g/mL, and the area under the plasma concentration-versus time curve from zero (0) h to infinity (infinity) increased from 87.86 to 151.52 h*mu g/mL, in tandem with the increase in fish body size. As fish body size increased, volume of distribution and total body clearance decreased. Conclusion. These results show that the pharmacokinetics of OTC vary depending on fish size. Therefore, there is a need to reveal the pharmacodynamic activity of OTC in rainbow trout of different body sizes.
Pharmacokinetic behaviour and pharmacokinetic-pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations
(2024.01.01) Altan, F.; Corum, O.; Corum, D.D.; Uney, K.; Terzi, E.; Bilen, S.; Sonmez, A.Y.; Elmas, M.
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.
Pharmacokinetic behaviour and pharmacokinetic-pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations
(2024) Altan, F.; Corum, O.; Durna Corum, D.; Uney, K.; Terzi, E.; Bilen, S.; Sonmez, A.Y.; Elmas, M.
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 (t1/2 ʎz), 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 µg/mL, 1.24 L/kg and 0.03 L/kg/h, respectively. The t1/2λz 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 µg/mL. The PK/PD integration showed that DO (20 mg/kg dose) for A. hydrophila and A. sobria with MIC90 ≤4 µg/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.
Pharmacokinetic behaviour and pharmacokinetic–pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations
(John Wiley and Sons Inc, 2024) Altan, F.; Corum, O.; Durna Corum, D.; Uney, K.; Terzi, E.; Bilen, S.; Sonmez, A.Y.; Elmas, M.
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 (t1/2ʎz), 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 µg/mL, 1.24 L/kg and 0.03 L/kg/h, respectively. The t1/2λz 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 µg/mL. The PK/PD integration showed that DO (20 mg/kg dose) for A. hydrophila and A. sobria with MIC90 ≤4 µg/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.
Pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid in rainbow trout (Oncorhynchus mykiss)
(2024.01.01) Corum, O.; Corum, D.D.; Marin, P.; Acar, O.F.; Aksoy, M.; Uney, K.
Background: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a nonsteroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties. Objectives: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acidwere investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 +/- 0.5 degrees C. Methods: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis. Results: The elimination half-life (t1/2 lambda z) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 mu g/mL, and 78.45% and 21.48%, respectively. Themean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent. Conclusions: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
Pharmacokinetics, Tissue Residues, and Withdrawal Times of Oxytetracycline in Rainbow Trout (Oncorhynchus mykiss) after Single- and Multiple-Dose Oral Administration
(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Corum, O.; Durna, C.D.; Terzi, E.; Uney, K.
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 °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 (t1/2ʎz) after IV and oral administration. The oral bioavailability of OTC was very low (2.80%). In multiple-dose treatment, t1/2ʎz, the area under the plasma concentration–time 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 °C, the WT calculated for muscle+skin was 56 days for Europe and 50 days for China, respectively. The t1/2ʎz (68.94 h) and time (68 h) above the 1 µg/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.