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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 and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous, intramuscular, subcutaneous, and oral administrations(WILEY, 2019) Corum, Orhan.; Corum, Duygu Durna.; Atik, Orkun.; Faki, Hatice Eser.; Altan, Feray.; Uney, Kamil.The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 +/- 45 g were used for the investigation. The study was performed in a crossover design (2 x 2 x 2 x 2) with a 15-day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed-phase high-performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half-life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 mu g/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady-state following IV administration were 0.13 L hr(-1) kg(-1) and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.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 Pharmacokinetics of marbofloxacin following intramuscular administration at different doses in sheep(ELSEVIER SCIENCE BV, 2019) Altan, Feray.; Corum, Orhan.; Corum, Duygu Durna.; Altan, Semih.; Uney, Kamil.The pharmacokinetics of marbofloxacin (MBX) was determined following the intramuscular administration at the doses of 2, 4, 6, and 10 mg/kg in twenty-four healthy sheep. In parallel design, sheep were randomized to 2, 4, 6, and 10 mg/kg dose groups of six animals per group. High performance liquid chromatography method for determination of MBX in sheep plasma was used. Pharmacokinetic parameters were calculated by a non-compartmental method. The dose-normalized the area under the concentration-versus-time curve (AUC(0-infinity)) and dose-normalized maximum plasma concentration (C-max) in 10 mg/kg dose group were significantly higher than other dose groups. The elimination half-life (t(1/2 lambda z)) of marbofloxacin in 10 mg/kg dose group was significantly longer than other dose groups. MBX exhibited dose-proportional pharmacokinetics and was well tolerated after 2, 4, 6 and 10 mg/kg doses in sheep. The 2, 4, 6, and 10 mg/kg doses of MBX could be administered in the treatment of infections caused by susceptible pathogens in sheep. However, additional studies are needed to identify whether MBX is efficient in sheep of naturally infected with susceptible bacteria.