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Öğe Pharmacokinetic/pharmacodynamic integration of marbofloxacin after oral and intravenous administration in rainbow trout (Oncorhynchus mykiss)(ELSEVIER, 2020) Corum, Orhan.; Terzi, Ertugrul.; Corum, Duygu Durna.; Kenanoglu, Osman Nezih.; Bilen, Soner.; Uney, Kamil.The pharmaco-kinetic/dynamic of marbofloxacin was investigated after single intravenous (IV) and oral administration of 10 mg/kg in 192 healthy rainbow trout at 13 +/- 1.2 degrees C. The plasma concentrations of marbofloxacin were determined by high-performance liquid chromatography-ultraviolet detection. After IV and oral administration, the plasma concentration-time data were described by a noncompartmental analysis. The minimal inhibitory concentration (MIC) of marbofloxacin against Yersinia ruckeri, Aeromonas hydrophila, Pseudomonas fluorescens and P. putida were determined by broth dilution method at 13 degrees C. After IV administration, the elimination half-life (t(1/2)(lambda z)), area under the concentration-versus time curve (AUC(0-infinity)), apparent volume of distribution at steady-state and total body clearance of marbofloxacin were 18.05 h, 354.63 h * mu g/mL, 0.65 L/kg and 0.03 L/h/kg, respectively. After oral administration, t(1/2 lambda z), AUC(0)(-infinity) the peak plasma concentration, time of maximum concentration and bioavailability were 27.51 h, 135.29 h * mu g/mL, 3.74 mu g/mL, 4 h and 38.15%, respectively. The respective MICs of marbofloxacin against Y. ruckeri, A. hydrophila, P. fluorescens and P. putida were determined as 0.02 mu g/mL, 2.5 mu g/mL, 2.5 mu g/mL and 5 mu g/mL, respectively. Following IV and oral administration of 10 mg/kg marbofloxacin, AUC/MIC and C-max/MIC values were above the target levels for Y. ruckeri, while this dose was not sufficient for A. hydrophila and Pseudomonas spp. Because the pharmacokinetics and pharmacodynamics of a drug in fish are significantly affected by temperature, the dosage regimen of marbofloxacin should be modified according to temperature.Öğe Pharmacokinetics and bioavailability of ceftriaxone in brown trout (Salmo trutta fario) after intravenous and intramuscular administration(ELSEVIER SCIENCE BV, 2019) Corum, Orhan.; Er, Ayse.; Corum, Duygu Durna.; Atik, Orkun.; Uney, Kamil.Ceftriaxone (CTX) is a third-generation cephalosporin that has proven to be effective in the treatment of infections caused by a wide range of gram-positive and gram-negative microorganisms. This study aimed to determine the plasma and muscle pharmacokinetics of CTX after its administration via the intravenous (IV) and intramuscular (IM) routes to brown trout (Salmo trutta fario) at temperatures of 10 degrees C-13 degrees C. In total, 140 healthy brown trout (body weight, 245 +/- 38 g) were used. The brown trout received single IV and IM injections of CTX at 25 mg/kg. The IV doses were injected into the caudal vein, whereas the IM doses were injected into the right epaxial muscles. The plasma and muscle tissue concentrations of CTX were measured using high-performance liquid chromatography. Pharmacokinetic parameters were calculated using noncompartmental methods. Following the IV administration of CTX, the elimination half-life (t1/2(sic)z), volume of distribution at steady state, total body clearance, and area under the concentration-time curve (AUC0-72) in plasma were 5.83 h, 0.09 L/kg, 0.02 L/h/kg, and 1079.46 h*mu g/mL, respectively. After the IM administration of CTX, plasma t1/2(sic)z, peak plasma concentration (Cmax), time to reach Cmax, and bioavailability were 22.78 h, 87.92 mu g/mL, 0.5 h, and 27.19%, respectively. The AUCmuscle/AHCplasma ratio following the IV administration was 0.02 and that following the IM administration was 0.04. CTX exhibited low bioavailability and prolonged t1/2(sic)z after the IM administration. The prolonged t1/2(sic)z of CTX could thus be beneficial in brown trout. Nevertheless, future studies that aim to determine the clinical efficacy and pharmacokinetics after repeated administration of CTX are warranted.Öğe Pharmacokinetics of cefquinome after single and repeated subcutaneous administrations in sheep(WILEY, 2019) Corum, Orhan.; Corum, Duygu Durna.; Er, Ayse.; Uney, Kamil.The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 +/- 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutaneously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concentrations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the single SC administration was 123.51 +/- 11.54%. The area under the curve (AUC(0-infinity)) and peak concentration following repeated doses (last dose) were higher than those observed after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is <= 1.0 mu g/ml in sheep.Öğe Use of intestine-related biomarkers for detecting intestinal epithelial damage in neonatal calves with diarrhea(AMER VETERINARY MEDICAL ASSOC, 2020) Ok, Mahmut.; Yildiz, Ramazan.; Hatipoglu, Fatih.; Baspinar, Nuri.; Ider, Merve.; Uney, Kamil.; Erturk, Alper.; Durgut, Murat K.; Terzi, Funda.OBJECTIVE To evaluate the usefulness of intestinal biomarkers in determining the presence of intestinal epithelial damage in neonatal calves with diarrhea caused by 4 etiologic agents. ANIMALS 40 neonatal calves that were healthy (n = 10) or had diarrhea (30). PROCEDURES The study was a cross-sectional study. Results of hematologic analyses and serum concentrations of intestinal fatty acid-binding protein (I-FABP), liver fatty acid-binding protein (L-FABP), trefoil factor 3 (TFF-3), Claudin-3 (CLDN-3), gamma-enteric smooth muscle actin (ACTG2), intestinal alkaline phosphatase (IAP), interleukin-8 (IL-8), platelet-activating factor (PAF), and leptin (LP) were compared among calves grouped according to whether they were healthy (control group; G-1) or had diarrhea caused by K99 Escherichia coli (G-2; n = 10), bovine rota-or coronavirus (G-3; 5 each), or Cryptosporidium spp (G-4; 10). RESULTS Across the 3 time points at which blood samples were obtained and evaluated, the groups of calves with diarrhea generally had markedly higher mean serum concentrations of L-FABP, TFF-3, IAP, IL-8, and LP, compared with the control group. In addition, G-2 also consistently had markedly higher mean serum concentrations of I-FAB and ACTG2 and lower mean serum concentrations of CLDN-3, compared with the control group. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that degree of intestinal epithelial damage differed among calves grouped by the etiologic agent of diarrhea and that such damage might have been more severe in calves with diarrhea caused by K99 E coli. Additionally, our results indicated that serum concentrations of I-FABP, L-FABP, TFF-3, IAP, IL-8, ACTG2, LP, and CLDN-3 were useful biomarkers of intestinal epithelial damage in calves of the present study.
