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Öğe Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep(Wiley, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Cetin, Gul; Irmak, Mehmet; Ceyhan, Hatice Rumeysa; Uney, KamilThe pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month- old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 +/- 0.91 kg), 6 months old (27.47 +/- 4.91 kg), and 12 months old (37.10 +/- 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (Vdss) and total body clearance (ClT) were significantly higher in 1- month- old (304.87 mL/kg and 16.57 mL/h/kg) than in 12- month- old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration- time curve from 0 to 72 h value of meloxicam was lower in 1- month- old (58.51 h*mu g/mL) compared to 12- month- old (92.59 h*mu g/mL) sheep. There was no difference in t1/ 2.z value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in Vdss and ClT in 12- month- old compared to 1- month- old sheep. Compared to 1- month- old and 12- month- old sheep, there was no difference in these parameters in 6- month- old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.Öğe Comparative Pharmacokinetics of Intravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep(Bentham Science Publ Ltd, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Uney, KamilBackground Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target-age animals. Objective To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC-UV and analyzed using a non-compartmental method. Results ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t(1/2 lambda z) and V-dss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC(0-infinity CIP)/AUC(0-infinity ENR) ratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion The most important pharmacokinetic changes associated with aging in sheep are decreased V-dss and t(1/2 lambda z) of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC(0-24)/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 mu g/mL and for S. aureus (>30) with MIC of 0.5 mu g/mL in all ages of sheep.Öğe Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain(Univ Karachi, 2019) Dik, Burak; Coskun, Devran; Bahcivan, Emre; Er, AyseThe aim of this study is to determine the effects of alone or combined usage of doxycycline and meloxicam on brain superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and matrix metalloproteinase (MMP)-9 levels of lipopolysaccharide (LPS)-induced brain inflammation. Totally 78 rats were divided into 5 groups; Healthy control (n=6), LPS (n=18, 0.05 mu g/mu L/rat, intracranially), LPS+D (n=18, LPS 0.05 mu g/mu L/rat, intracranially and doxycycline 40 mg/kg, intraperitoneally), LPS+M (n=18, LPS 0.05 mu g/mu L/rat, intracranially and meloxicam 2 mg/kg, intraperitoneally), LPS+Combination (n=18, LPS 0.05 mu g/mu L/rat, intracranially and simultaneously both drug combination) groups. Animals were euthanized at 1, 3 and 6 hours following injections and the brains were removed. Brain SOD, CAT, MDA and MMP-9 levels were determined by ELISA reader. Parameters of LPS groups generally different from Healthy control group. When compared to LPS group, increased SOD level of LPS+D at 3 hours and CAT levels of LPS+M and LPS+D groups were determined (P<0.05) at 3 and 6 hours, respectively. In addition, all treatments statistically significantly (P<0.05) decreased MMP-9 levels at 6 hours. In conclusion, doxycycline and meloxicam may show antioxidant effect via increasing antioxidant enzyme production in the brain; however combined usage of drugs may show more beneficial effect for neuroinflammation.Öğe Effect of Age on the Pharmacokinetics of Marbofloxacin Following Intravenous Administration in Calves(Wiley, 2024) Corum, Orhan; Yuksel, Murat; Coskun, Devran; Corum, Duygu Durna; Kartal, Serafettin; Cellat, Mustafa; Uney, KamilThe aim of this study was to compare the pharmacokinetics of marbofloxacin after intravenous (IV) administration of a single dose of 10 mg/kg to calves of different ages. The study was carried on 1- (n = 6), 2- (n = 6), and 4-month-old (n = 6) Montofon calves. Plasma concentrations of marbofloxacin were measured using HPLC, and pharmacokinetic data were calculated by non-compartmental analysis. The elimination half-life (t(1/2 lambda z)), volume of distribution at steady state (V-dss), total clearance (Cl-T), and area under the concentration-versus time curve (AUC(0-infinity)) values of marbofloxacin in 1-month-old calves were 10.62 h, 1.03 L/kg, 0.08 L/h/kg, and 127.90 h*mu g/mL, respectively. While the t(1/2 lambda z) (from 10.62 to 3.36 h) and AUC(0-infinity) (from 127.90 to 47.35 h*mu g/mL) decreased in parallel with the age of the calves, Cl-T (from 0.08 to 0.21 L/h/kg) increased. The V-dss of marbofloxacin was higher in 1- and 2-month-old calves compared to 4-month-old calves. After IV administration of marbofloxacin at a dose of 10 mg/kg, an fAUC(0-24)/MIC90 ratio of >= 125 was obtained for bacteria with MIC90 values of <= 0.60, <= 0.39 and <= 0.27 mu g/mL in 1-, 2-, and 4-month-old calves, respectively. These results show that the antibacterial effect of marbofloxacin, which has concentration-dependent activity, decreases due to age-related pharmacokinetic changes and that the 10 mg/kg dose should be reviewed according to the MIC90 value of the bacteria.Öğe Effect of Body Size on Plasma and Tissue Pharmacokinetics of Danofloxacin in Rainbow Trout (Oncorhynchus mykiss)(Mdpi, 2024) Uney, Kamil; Corum, Duygu Durna; Marin, Pedro; Coskun, Devran; Terzi, Ertugrul; Badillo, Elena; Corum, OrhanDanofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 +/- 0.5 degrees C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t1/2 lambda z), volume of distribution (Vdarea/F), total clearance (CL/F), peak concentration (Cmax), and area under the plasma concentration-time curve (AUC0-last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 mu g/mL, and 82.46 h center dot mu g/mL, respectively. Plasma t1/2 lambda z, AUC0-last and Cmax increased concomitantly with trout growth, whereas CL/F and Vdarea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. Cmax and AUC0-last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 mu g/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue.Öğe Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain(Mashhad Univ Med Sciences, 2020) Er, Ayse; Coskun, Devran; Bahcivan, Emre; Dik, BurakObjective(s): Prevention of inflammation in early stages will be useful in maintaining vitality of the organism. The objective of this study was to evaluate the effects of doxycycline (DOX) or meloxicam (MLX) monotherapy and combination therapy on the levels of inflammatory mediators in the brain tissues of rats with Escherichia coli lipopolysaccharide (LPS)-induced brain inflammation. Materials and Methods: Seventy-eight rats were divided into the following groups: control (n=6), LPS (0.5 mu g/10 mu l intracranial) (n=18), LPS (0.5 mu g/10 mu l intracranial)+DOX (40 mg/kg intraperitoneal) (n=18), LPS (0.5 mu g/10 mu l intracranial)+MLX (2 mg/kg intraperitoneal) (n=18) and LPS (0.5 mu g/10 mu l intracranial)+DOX (40 mg/kg intraperitoneal)+MLX (2 mg/kg intraperitoneal) (n=18) groups. Brain tissues were harvested from all rats in the control group and from six rats each in the four experimental groups at 1, 3 and 6 hr under anaesthesia. The levels of tumor necrosis factor alpha (TNF alpha), interleukin 4 (IL-4), IL-6, IL-10, IL-17, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 3 (TIMP-3) and cyclooxygenase 2 (COX-2) in the brain tissues were measured using ELISA kits with ELISA device. Results: LPS administration increased proinflammatory cytokines (TNF, IL-6, IL-17), and MMP-3 levels and decreased anti-inflammatory cytokines (IL-10, IL-4), and BDNF levels. The lowest TNF alpha levels were detected in the LPS+MLX group (P<0.05). All the drug treatment groups showed decreased IL-17 and COX-2 levels compared to the LPS groups. Conclusion: DOX or MLX monotherapy exerts neuroprotective effects against brain inflammation by decreasing proinflammatory cytokine levels and by increasing anti-inflammatory cytokines levels.Öğe Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep(Wiley, 2021) Cetin, Gul; Durna Corum, Duygu; Corum, Orhan; Atik, Orkun; Coskun, Devran; Uney, KamilIn this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 +/- 0.3 years and 44 +/- 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t(1/2 lambda z)), area under the plasma concentration-time curve from zero (0) hours to infinity (infinity) (AUC(0-infinity)), total clearance (Cl-T), and volume of distribution at steady state were 1.42 h, 182.41 h*mu g/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t(1/2 lambda z) and AUC(0-infinity) of ceftriaxone, they significantly reduced the Cl-T. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of <= 0.75 and <= 1 mu g/mL, respectively, in sheep with an inflammatory condition.Öğe Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)(Wiley, 2022) Corum, Orhan; Uney, Kamil; Corum, Duygu Durna; Atik, Orkun; Coskun, Devran; Zhunushova, Aidai; Elmas, MuammerThe aim of the study was to determine the effect of ketoprofen (2 mg/kg) on the intravenous pharmacokinetics of ganciclovir (10 mg/kg) in chukar partridges (Alectoris chukar). Eight clinically healthy partridges were used in the study. The study was performed in two periods using a cross-over design following a 15-day drug washout period. Plasma concentrations of ganciclovir were determined using the high-pressure liquid chromatography-ultraviolet detector and analyzed by non-compartmental analysis. The elimination half-life (t(1/2 lambda z)), area under the concentration-time curve (AUC(0-infinity)), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*mu g/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t(1/2 lambda z) and AUC(0-infinity) of ganciclovir by 78% and 108%, respectively, and while decreased Cl-T by 53%. The increased plasma concentration and prolonged elimination half-life of ganciclovir caused by ketoprofen may result in the prolonged duration of action and therapeutic effect of ganciclovir. However, the concomitant use requires determination of the pharmacokinetics of ketoprofen and the safety of both drugs.Öğe Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep(Wiley, 2020) Coskun, Devran; Corum, Orhan; Yazar, EnverThe purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 mu g/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the t1/2 lambda z, AUC(0-infinity), Cl-T, and V-dss were 2.87 hr, 34.73 hr x mu g/ml, 0.29 L hr(-1) kg(-1), and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the Cl-T of marbofloxacin decreased, AUC(0-infinity) increased, and t1/2 lambda z and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 mu g/ml for E. coli, 0.016 to >16 mu g/ml for M. haemolytica, 0.016-1 mu g/ml for P. multocida, 0.016-0.25 mu g/ml for K. pneumoniae, 0.031-0.063 mu g/ml for Salmonella spp., and 0.031-1 mu g/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.Öğe Effect of Xylazine on Pharmacokinetics and Physiological Efficacy of Intravenous Carprofen in Castrated Goats Kids(Mdpi, 2023) Uney, Kamil; Yuksel, Murat; Corum, Duygu Durna; Coskun, Devran; Turk, Erdinc; Dingil, Hasan Basri; Corum, OrhanCarprofen can be used in the castration process of male goats due to its low side effects, long elimination half-life, and long-term effect. However, no studies were found on the pharmacokinetics and physiological efficacy of carprofen when employed for castration in male goats. The aim of this study was to determine the effect of xylazine (0.05 mg/kg, intramuscular) on the pharmacokinetics and physiological efficacy following intravenous administration of carprofen (4 mg/kg, intravenous) in male goat kids castrated using the burdizzo method. Thirty male Kilis goat kids (5-6 months and 18-30 kg of body weight) were randomly assigned to five groups (n = 6) as follows: healthy control (HC), castration control (CAST), castration+carprofen (CAST+CRP), castration+xylazine (CAST+XYL), and castration+xylazine+carprofen (CAST+XYL+CRP). Plasma concentrations of carprofen were analyzed via a non-compartmental method. Physiological parameters including serum cortisol, scrotal temperature, rectal temperature, and scrotal circumference were determined. Xylazine caused a decrease in the volume of distribution and clearance and an increase in the area under the curve of carprofen in CAST+XYL+CRP group (p < 0.05). The mean cortisol concentrations in CAST+CRP and CAST+XYL remained lower compared to CAST (p < 0.05). The mean cortisol concentrations in CAST+XYL+CRP were lower than in CAST+CRP and CAST+XYL (p < 0.05). In addition, the effect of carprofen administration alone on reducing the initial cortisol response to castration was observed from 6 to 48 h, while in combination with xylazine, it was observed immediately up to 48 h. No treatment differences were observed in rectal temperature, scrotal temperature, and scrotal circumference (p > 0.05). Xylazine caused an increase in plasma concentration and a decrease in clearance of carprofen after co-administration. However, when the effect of the combined administration of carprofen with xylazine on cortisol is evaluated, their combined use in castration process may be beneficial.Öğe Effects of Boron on Learning and Behavioral Disorders in Rat Autism Model Induced by Intracerebroventricular Propionic Acid(Springernature, 2024) Alacabey, Nur Akman; Coskun, Devran; Atessahin, AhmetAutism spectrum disorder is a neurodevelopmental disorder in which learning, communication, and social interaction are impaired. Research has sought to minimize the neural impairments associated with autism spectrum disorder and improve the quality of life. Recent studies suggest that boron may benefit nerve cells, with effects varying depending on the dosage. This study explored the impact of boron, administered as boric acid, on behavioral, biochemical, and histopathological parameters in a rat model of autism induced by propionic acid (PPA). Thirty-two male Sprague-Dawley rats were divided into control, autism model, and boron-treated groups. Behavioral tests were conducted pre- and post-PPA induction, with brain tissue analyzed post-euthanasia. Proinflammatory cytokines (tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6)) and brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus. Histopathological evaluations were conducted on the hippocampus and cerebellum. Autism model rats displayed impaired learning, elevated BDNF and cytokine levels, microglial and astrocytic activation, and decreased Purkinje cell count. The boron-treated groups showed improvements, particularly with the 4 mg/kg dose. This dose enhanced learning and social interaction, reduced proinflammatory cytokine levels, prevented microglial and astrocytic activation, and increased Purkinje cell count. Boron treatment exhibited neuroprotective potential, ameliorating autism spectrum disorder deficits by modulating cytokines, BDNF, microglia, and astrocytes, with low doses yielding pronounced effects.Öğe Effects of Boron on Learning and Behavioral Disorders in Rat Autism Model Induced by Intracerebroventricular Propionic Acid (Oct, 10.1007/s12011-024-04417-9, 2024)(Springernature, 2024) Alacabey, Nur Akman; Coskun, Devran; Ceribasi, Songul; Atessahin, Ahmet[Abstract Not Available]Öğe Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration(Mdpi, 2023) Corum, Orhan; Uney, Kamil; Terzi, Ertugrul; Corum, Duygu Durna; Coskun, Devran; Altan, Feray; Elmas, MuammerSimple Summary Doxycycline, an approved aquacultural antibiotic, is extensively used in the treatment of bacterial diseases in fish. Since fish are poikilothermic organisms, their body temperature and metabolic rate are primarily influenced by the temperature of the water. Therefore, temperature may be affected by pharmacokinetic behavior and withdrawal times of drugs. The current study was undertaken to look at the differences in pharmacokinetics, tissue residues, and withdrawal times of doxycycline following oral administration in rainbow trout reared at 10 and 17 & DEG;C. The increment of water temperature from 10 to 17 & DEG;C decreased the elimination half-life, the body clearance, and the distribution volume of doxycycline and increased plasma concentrations. The withdrawal times for plasma and tissues decreased with the temperature increase. The results contributed to the determination of an optimal dosing regimen and the safe consumption of edible tissues in rainbow trout that were administered doxycycline and reared at different temperatures. The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 & DEG;C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 & DEG;C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration-time curve from 173.23 to 240.96 h * & mu;g/mL, and increased the peak plasma concentration from 3.48 to 5.50 & mu;g/mL. At 10 and 17 & DEG;C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 & mu;g/kg) and in Japan (50 & mu;g/kg), the withdrawal times of doxycycline at 10 and 17 & DEG;C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.Öğe Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats(Univ Fed Rio Grande Do Sul, 2018) Corum, Orhan; Ozdemir, Ozgur; Hitit, Mustafa; Corum, Duygu Durna; Coskun, Devran; Er, AyseBackground: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long term. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents, can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented by using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective of this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage. Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline, kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normal saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for 20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular dilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates were observed in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifylline groups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameters within reference ranges (P < 0.05). Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifylline inhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although this reduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascular inflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline prevented tubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also ameliorated amikacin-or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protective effects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulating the production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatory effects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs in the present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/or are dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemical parameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggested that kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.Öğe Pharmacokinetics and bioavailability of carprofen in sheep(Wiley, 2022) Coskun, Devran; Corum, Orhan; Durna Corum, Duygu; Uney, Kamil; Elmas, MuammerThe aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV. Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t(1/2 lambda z), Cl-T, and V-dss were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C-max(obs) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 mu g/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route.Öğe Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration(Elsevier, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Uney, KamilObjective To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg(-1) in Pekin ducks.Study design Randomized experimental trial.Animals A total of 18 clinically healthy male Pekin ducks.Methods Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg(-1)) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.Results No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg(-1) and 6.68 mL kg(-1) hour(-1), respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (C-max), time to reach C-max and bioavailability (p < 0.05).Conclusions and clinical relevance Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.Öğe Pharmacokinetics and Plasma Protein Binding of Flunixin in Rainbow Trout (Oncorhynchus mykiss)(Wiley, 2024) Uney, Kamil; Corum, Orhan; Corum, Duygu Durna; Coskun, Devran; Sakin, Fatih; Elmas, MuammerFlunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout (Oncorhynchus mykiss) maintained at 12 +/- 0.6 degrees C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High-pressure liquid chromatography-ultraviolet was employed to quantify flunixin concentrations. The elimination half-life (t(1/2 lambda z)) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t(1/2 lambda z) was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 +/- 0.41 mu g/mL at 4 h for oral administration and 13.98 +/- 0.86 mu g/mL at 2 h for IM administration. The in vitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 +/- 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.Öğe Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep(Wiley, 2022) Corum, Orhan; Coskun, Devran; Corum, Duygu Durna; Ider, Merve; Yildiz, Ramazan; Ok, Mahmut; Uney, KamilThe aim of this study was to determine the pharmacokinetics of carprofen following single and repeated intravenous (IV) administrations at 1.4 and 4 mg/kg doses in sheep. The study was carried out on twelve sheep in two experiments as single- and multiple-dose pharmacokinetics. In experiment 1, carprofen was administered via IV at single doses of 1.4 (n = 6) and 4 mg/kg (n = 6) in a randomized parallel design. In experiment 2, the same dose groups in experiment 1 following the 21-day washout period received intravenously carprofen every 24 h for 5 days. Plasma concentrations were measured using high-performance liquid chromatography-UV and analyzed by a two-compartment open model. After the single administration of 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 0.62 h, 27.57 h, 38.78 h, 2.72 ml/h/kg, 105.26 ml/kg, and 515.12 h*mu g/ml, respectively. Carprofen at a single dose of 4 mg/kg showed prolonged t(1/2el) and MRT, and increased V-dss. On day 5 after the repeated administration of the 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 1.12 h, 57.48 h, 82.18 h, 0.55 ml/h/kg, 45.43 ml/kg, and 2532 h*mu g/ml, respectively. Carprofen at a repeated dose of 4 mg/kg showed increased Cl-T and V-dss and decreased AUC/dose. Although the long t(1/2 lambda z) in single and multiple IV dose studies suggest the possibility of its effective use, the IV route may not be practical in sheep. Therefore, oral and subcutaneous routes of carprofen in sheep would be more valuable in clinical settings.Öğe Pharmacokinetics of cefquinome in rainbow trout (Oncorhynchus mykiss) after intravascular, intraperitoneal, and oral administrations(Wiley, 2022) Corum, Duygu Durna; Corum, Orhan; Terzi, Ertugrul; Coskun, Devran; Bilen, Soner; Cetin, Gul; Uney, KamilThis study aimed to determine the pharmacokinetics and bioavailability of cefquinome in rainbow trout (Oncorhynchus mykiss) following intravascular (IV), intraperitoneal (IP), and oral (PO) administrations at 14 +/- 1 degrees C. In this study, three hundred and six clinically healthy rainbow trout (110-140 g) were used. The fish received single IV, IP, and PO injections of cefquinome at 10 mg/kg dose. The plasma concentrations of cefquinome were measured using HPLC-UV and were evaluated using non-compartmental analysis. Cefquinome was measured up to 96 h for PO route and 144 h for IV and IP routes in plasma. Following IV administration, t(1/2 lambda z), Cl-T, and V-dss were 18.85 h, 0.037 L/h/kg, and 0.84 L/kg, respectively. The C-max of IP and PO routes was 9.75 and 1.64 mu g/ml, respectively. The bioavailability following IP and PO administrations was 59.46% and 12.33%, respectively. Cefquinome at 10 mg/kg dose may maintain T > MIC above 40% at 72 and 96 h intervals, respectively, following the IP and IV routes for bacteria with MIC values of <= 2 mu g/ml and at 24 h intervals following the PO route for bacteria with MIC value of <= 0.75 mu g/ml. However, further studies are needed to determine in vitro and in vivo antibacterial efficacy and multiple dosage regimens of cefquinome against pathogens isolated from rainbow trout.Öğe Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep(Wiley, 2024) Gungor, Huseyin; Corum, Orhan; Corum, Duygu Durna; Kumru, Alper Serhat; Yilmaz, Gokhan; Coskun, Devran; Coskun, AlparslanThe aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that V(dss )decreased and C-0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 mu g/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of >= 1 mg/kg in sheep.
