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Öğe Alcoholic extract of Tarantula cubensis induces apoptosis in MCF-7 cell line.(Allied Acad, 2017) Er, Ayse; Corum, Orhan; Corum, Duygu; Hitit, Mustafa; Donmez, Huseyin; Guzeloglu, AydinTarantula cubensis Alcoholic Extract (TCAE) is a homeopathic agent used for treating many disorders. This study aimed to define the effects of TCAE on the breast carcinoma cell line (MCF-7). After various concentrations (10, 20, 40, 80 and 160 mu l/ml) of TCAE were applied to MCF-7 cells and the human embryonic kidney cell line (HEK293), the cells were incubated for 1, 3, 6, 9, 12, 24 and 48 h, followed by analysis by MTT assays. According to the results of the MTT assays, cells treated with 20 or 40 mu l/ml TCAE for 6 h were applied to apoptosis analysis by flow cytometry. Secreted levels of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-10, Interferon-gamma (IFN gamma), Transforming Growth Factor beta (TGF beta), and Nuclear Factor-kappa B (NF-kappa B) were measured using ELISAs. TNF alpha and TGF beta levels increased while IL-6 and IL-10 levels fluctuated in MCF-7 cells. In conclusion, our study suggests that TCAE may change the normal cancer physiology and lead to cell death by activating apoptosis in MCF-7 cells.Öğe Cardiac Safety of Diclofenac at a Single Dose in Ram(Hindawi Ltd, 2013) Er, Ayse; Dik, Burak; Corum, Orhan; Cetin, GulNonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), andmuscular (creatine kinase) damagemarkers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep.Öğe CHANGES IN NOVEL GASTROINTESTINAL AND RENAL INJURY MARKERS IN THE BLOOD PLASMA OF SHEEP FOLLOWING INCREASING INTRAVENOUS DOSES OF TOLFENAMIC ACID(Akademiai Kiado Zrt, 2019) Yildiz, Ramazan; Corum, Orhan; Atik, Orkun; Corum, Duygu Durna; Altan, Feray; Ok, Mahmut; Uney, KamilThe administration of high doses of non-steroidal anti-inflammatory drugs (NSAID), such as tolfenamic acid (TA), has undesirable effects on different organs. Some novel biomarkers have been reported that can determine the gastrointestinal and renal injury caused by a high dose of NSAIDs or other toxic substances. This study was aimed at determining the changes in gastrointestinal (TFF2 and HYP), renal (NGAL and KIM-1) and cardiac (cTn-I, CK-MB) injury markers after the use of increasing intravenous doses of TA in sheep. TA was administered intravenously to groups of six sheep each, at the dose levels of 0 (Group 0, i.e., G0), 2 (G2), 4 (G4), 8 (G8) and 16 (G16) mg/kg. The concentrations of the studied biomarkers were measured at 3, 9, 18 and 36 h after administration of TA. The TFF2 and NGAL concentrations in G16 were found to be significantly higher (P < 0.05) than in the other groups except for G8 at different sampling times. HYP concentration in G16 was observed to be significantly (P < 0.05) lower than that in all other groups at 36 h. KIM-1 level in G16 was significantly (P < 0.05) higher than in all other groups at different sampling times. An increase in the renal markers, KIM-1 and NGAL, in G8 was observed before any change in plasma creatinine and urea. The cardiac marker cTn-I in G16 was significantly (P < 0.05) higher than in other groups at different sampling times. The results showed that the novel biomarkers (HYP, TFF2, NGAL, and KIM-1) can be used to determine gastric and renal injury in sheep.Öğe Effect of benzylpenicillin on intravenous pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans)(Wiley, 2020) Corum, Duygu D.; Corum, Orhan; Atik, Orkun; Faki, Hatice E.; Altan, Feray; Uney, KamilThe aim of this study was to determine the effect of benzylpenicillin on the pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans). Six clinically healthy red-eared slider turtles weighing 400 and 580 g were used for the study. Acyclovir (40 mg/kg) and benzylpenicillin (30 mg/kg) were administered intravenously to turtles. In the study, the cross-pharmacokinetic design (2 x 2) with a 30-day washout period was performed in two periods. Plasma concentrations of acyclovir were assayed using the high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by two-compartment open pharmacokinetic model. Following the administration of acyclovir alone, elimination half-life (t(1/2)(beta)), area under the plasma concentration-time curve (AUC), total clearance (Cl-T), and volume of distribution at steady-state (V-dss) were 20.12 hr, 1,372 hr * mu g/mL, 0.03 L hr(-1) kg(-1), and 0.84 L/kg, respectively. Benzylpenicillin administration increased t(1/2)(beta), AUC, and V-dss while decreased Cl-T of acyclovir. These results showed that benzylpenicillin changed the pharmacokinetics of acyclovir following simultaneous administration in turtles. However, further research is needed to determine molecular mechanism of interaction in turtle.Öğe Effect of Corynebacterium cutis Lysate on Serum Oxidative Stress and Plasma Prostaglandin F2? Metabolite Levels(Univ Fed Rio Grande Do Sul, 2014) Er, Ayse; Dik, Burak; Corum, OrhanBackground: The Corynebacterium cutis lysate is commercial product. Unbalance between oxidants and antioxidants cause oxidative stress and lipid peroxidation in the cell. Macrophages phagocytose large pieces of bacteria and synthesize cytokines. In addition to the benefi cial results of the drug have side effects. Since changes in biochemical parameters refl ect structural dysfunction in the organism, monitoring changes of these parameters is a way to keep track of side effects. The aim of this study was to determine the effect of Corynebacterium cutis lysate on serum thiobarbituric acid-reactive substances (TBARS) and plasma 13,14-dihydro-15-keto-prostaglandinF2a (PGM) levels in sheep. Materials, Methods & Results: Six Merino crossbred ewes (aged > 2 years, weight 40-60 kg) were used in this study. The procedures were approved by the Ethics Committee. A dose of 8 mg (0.4 mL) of commercial Corynebacterium cutis lysate was subcutaneously injected to each of the 6 Merino crossbred ewes. Blood specimens were taken from the sheep prior to injection (day 0, control) and after the injection on days 1, 2, 3, and 4. The levels of serum TBARS and plasma PGM were determined using an Enzyme Linked Immunosorbent Assay (ELISA) reader. The values of the hemogram [ white blood cells (WBC), red blood cells (RBC), platelets (PLT), hematocrit (HTC), and hemoglobin (HBG)] were assessed using a blood cell count apparatus. The levels of plasma creatine kinase-MB (CK-MB), serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine, and cholesterol were determined on an autoanalyzer. The data obtained were analyzed using ANOVA and Scheffe's test as a post hoc test (SPSS 19.0). A P < 0.05 value was taken as the cut-off value for statistical signifi cance. An increase (P < 0.05) in the levels of plasma PGM and serum cholesterol was detected when compared to the control samples, but there was no statistically signifi cant (P > 0.05) change in the other parameters. Discussion: The Corynebacterium cutis lysate is a commercial product and used in cattle, newborn calves, sheep, and poultry as an immunostimulant against infections and to increase body resistance in times of stress. Corynebacterium cutis lysate increased (P < 0.05) in plasma PGM and serum cholesterol levels compared to the control group. Detailed studies dealing with the effect of Corynebacterium cutis lysate on PGM and TBARS are not available in the literature. There is a balance between oxidants and antioxidants in the organism. Unbalance between oxidants and antioxidants caused by increased production of oxidizing species leads to oxidative stress and lipid peroxidation in the cells. The levels of TBARS or malondialdehyde are used in order to determine lipid peroxidation. The levels of serum TBARS, malondialdehyde and PGM increased in experimental infection models. Macrophages phagocytose large pieces of bacteria such as Corynebacterium cutis lysate and this case triggers the synthesis of cytokines by macrophages. Cholesterol metabolism may change in infections, and high levels of cholesterol were determined in test subjects after injection of LPS. Lipid metabolism may be affected by stimulants of the immune system, such as Corynebacterium cutis lysate. In conclusion, Corynebacterium cutis lysate has no effect on the oxidative status and number of blood cells and organ (heart, liver and kidney) damage markers in sheep and it may increase plasma PGM level by stimulating the immune system.Öğe The effects of Mannheimia haemolytica and albendazole on marbofloxacin pharmacokinetics in lambs(Springer, 2019) Altan, Feray; Ipek, Duygu Neval Sayin; Corum, Orhan; Alp, Simten Yesilmen; Ipek, Polat; Uney, KamilThe study aimed to define the effects of M. haemolytica and a single oral dose of albendazole on the single-dose pharmacokinetics of marbofloxacin in lambs. The pharmacokinetic-pharmacodynamic integration of marbofloxacin was applied to describe a 3 mg/kg intramuscular dose in lambs. The 6 healthy and 12 naturally infected with M. haemolytica lambs (Akkaraman, males weighing 10-15 kg and aged 2-3 months) were used in this study. In the marbofloxacin group, 6 healthy lambs received marbofloxacin. In the albendazole group after 2 weeks washout period, the same animals received marbofloxacin on 1 h after albendazole. In the diseased marbofloxacin group, 6 lambs naturally infected with M. haemolytica received marbofloxacin. In the diseased albendazole group, 6 lambs naturally infected with M. haemolytica received marbofloxacin on 1 h after albendazole. The marbofloxacin and albendazole were administered each as a single dose of 3 mg/kg intramuscular and 7.5 mg/kg oral, respectively, in the respective groups. Plasma concentration of marbofloxacin was measured with HPLC-UV and pharmacokinetic parameters were analyzed by non-compartmental model. Albendazole did not change the pharmacokinetic profiles of marbofloxacin in healthy and diseased lambs. However, M. haemolytica affected the pharmacokinetics of marbofloxacin in diseased lambs, AUC(0-24)/MIC90 ratio was not found to be higher than 125, but C-max/MIC90 ratios was found to be higher than 10 for an MIC value of 0.25 mu g/mL in all groups. The marbofloxacin dose described in this study may not be effective for the treatment of infections due to M. haemolytica in lambs, with MIC <= 0.25 mu g/mL.Öğe Halofuginone may suppresses azoxymethane-induced serum tumor necrosis factor-a synthesis and aberrant crypt foci progression in rat colon(Agricultural Research Communication Centre, 2017) Corum, Orhan; Ozdemir, Ozgur; Yazar, EnverThe aim of this research was to investigate the effect of halofuginone on the progression of azoxymethane-induced colon cancer in rats. A total of 38 male Wistar albino rats were divided into 4 groups: Control (n=8), Halofuginone (n= 10, 0.4 mg/kg, PO, SID), Cancer (n=10, azoxymethane, 15 mg/kg, IP, once a week for two weeks) and Cancer + Halofuginone (n=10). After 18 weeks, blood samples were taken under anesthesia and all animals were sacrificed. Aberrant crypt foci in the colon were stained with methylene blue. Blood cytokines, thiobarbituric acid reactive substances, 13,14-dihydro-15-ketoprostaglandin F2 alpha levels, hemogram and biochemical values were measured. The tumor necrosis factor-a level in the Cancer group was higher (P<0.05) than in other groups, while higher numbers of aberrant crypt foci were found in the Cancer group compared with the Cancer + Halofuginone group (P<0.05). In summary, it may be stated that halofuginone may warrant evaluation as a supportive drug in the treatment of colon cancer in the future.Öğe Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep(Wiley, 2020) Altan, Feray; Corum, Orhan; Yildiz, Ramazan; Faki, Hatice Eser; Ider, Merve; Ok, Mahmut; Uney, KamilIn this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 +/- 0.3 years and 53.5 +/- 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t(1/2 beta)), total body clearance (Cl-T), volume of distribution at steady state (V-dss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h(-1) kg(-1), 1.66 L/kg and 8.91 hr*mu g/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t(1/2 beta) and AUC of moxifloxacin, they significantly reduced the Cl-T and V-dss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.Öğe Investigation of the Effect of Tarantula cubensis Extract on Acute Phase Response(Univ Fed Rio Grande Do Sul, 2016) Corum, Orhan; Er, Ayse; Dik, BurakBackground: Tarantula cubensis alcoholic extract is used to accelerate wound healing and to relieve edema in many animal species. In addition, it may be useful for many infectious diseases. Considering to these effects, it is believe that these effects may be on immune system. Cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma) secreted by immune cells and acute phase proteins (haptoglobin, alpha 1 acid glycoprotein, serum amyloid A) secreted by liver play role in acute phase response. The aim of the present study was to determine the effect of Tarantula cubensis alcoholic extract on cytokine and acute phase protein levels in sheep. Materials, Methods & Results: Tarantula cubensis alcoholic extract (6 mL/sheep, subcutaneously, single dose) was administered to 6 healthy sheep. Blood samples were obtained before (0 h) and after treatments at 2, 4, 8, 12, 24 and 48 h. Then, blood samples were centrifuged to obtain serum samples. Acute phase cytokines such as serum tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma and acute phase proteins such as haptoglobin, alpha 1 acid glycoprotein and serum amyloid-A concentrations were determined with commercially available kits on ELISA reader. Administration of Tarantula cubensis alcoholic extract caused fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma levels in sheep. In addition, levels of haptoglobin, alpha 1 acid glycoprotein, serum amyloid A showed fluctuations. But, these fluctuations in acute phase cytokines and acute phase proteins were not statistically significant (P > 0.05). Discussion: Tarantula cubensis alcoholic extract, homeopathic medicine, is used trauma, retentio secundinarium, tendinitis, bluetongue, foot and mouth, metritis and arthritis in many animal species including sheep. Cytokines, secreted against various stimulus including infectious diseases, play role in wound healing and in the regulation of the immune system. In current study, administration of Tarantula cubensis alcoholic extract lead to fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma levels, but these changes were not statistically significant (P > 0.05). Non-statistical fluctuations in cytokines result from inadequate immunological response of sheep against to Tarantula cubensis alcoholic extract. Also, use of molecular analysis techniques may be changed these results. Acute phase proteins are significantly secreted from the liver during the acute phase response. In current study, administration of Tarantula cubensis alcoholic extract in sheep caused non-statistifical fluctuations on haptoglobin, alpha 1 acid glycoprotein and serum amyloid A levels (P > 0.05). Tumor necrosis factor alpha and interleukin-1 beta stimulate synthesis of interleukin-6. Interleukin-6 provides synthesis of acute phase proteins in liver. Non-statistical fluctuations in acute phase proteins result from inadequate stimulus of IL-6. In conclusion, it may be stated that administration of Tarantula cubensis alcoholic extract has no distinctive effect on the acute phase response. However, when Tarantula cubensis alcoholic extract is administered repeated times or other acute phase parameters are evaluated, different results may be observed.Öğe Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves(Wiley, 2019) Corum, Orhan; Yildiz, Ramazan; Ider, Merve; Altan, Feray; Ok, Mahmut; Uney, KamilThe aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 1.85 and 3.31 hr, area under the plasma concentration-time curve (AUC(0-infinity)) 15.74 and 174 hr * mu g/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr(-1) kg(-1), respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 mu g/ml, time to reach peak concentration 1 and 1.5 hr, t(1/2 lambda z) 4.74 and 3.62 hr, and AUC(0-infinity) 22.75 and 147 hr * mu g/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of <= 0.5 and <= 4 mu g/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.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, KamilThe 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 and bioavailability of marbofloxacin in lambs following administration of intravenous, intramuscular and subcutaneous(Elsevier Science Bv, 2018) Altan, Feray; Corum, Orhan; Corum, Duygu Durna; Atik, Orkun; Uney, KamilIn this study, the pharmacokinetic disposition and bioavailability of marbofloxacin (MB) were determined in lambs after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at a dose of 3 mg/kg. The plasma concentration of MB was measured using high-performance liquid chromatography-UV, and the pharmacokinetic parameters were analyzed using a non-compartmental analysis. Following IV, IM, and SC administrations, the mean terminal half-life (t(1/2 lambda z)) was 11.48, 12.64, and 24.86 h, respectively, and the mean residence time (MRT) was 7.27, 7.81, and 10.11 h, respectively. The bioavailability (F) was 96.01 and 126.39%, after IM and SC administration, respectively. This study showed that SC administration of MB at a dose of 3 mg/kg exhibited flip-flop pharmacokinetics in lambs. These results suggested that MB could be useful in the treatment of severe systemic infections, such as those with M. haemolytica (MIC = 0.035 mu g/mL), in lambs since high AUC(0.24)/MIC and C-max/MIC ratios were achieved after IV and IM administration at 3 mg/kg. However, MB administration (3 mg/kg) via the IV, IM, and SC routes might not be effective in the treatment of respiratory infections caused by organisms with MIC90 value in lambs.Öğe Pharmacokinetics of ceftriaxone following single ascending intravenous doses in sheep(Elsevier Science Bv, 2018) Corum, Duygu Durna; Corum, Orhan; Altan, Feray; Faki, Hatice Eser; Bahcivan, Emre; Er, Ayse; Uney, KamilThe objective of this study was to evaluate the pharmacokinetics of CTX following intravenous administration of ascending doses in sheep. In this study, six clinically healthy Akkaraman sheep (2.4 +/- 0.4 years and 50 +/- 3 kg of body weight) were used. CTX was administered intravenously to each sheep at 20, 40, and 80 mg/kg doses in a crossover design with a 15-day washout period. Plasma concentrations of CTX were measured using the high-performance liquid chromatography-UV method. Pharmacokinetic parameters were calculated by non-compartmental analysis. CTX was well tolerated following administration at 20, 40, and 80 mg/kg doses. The elimination half-life following administration of 40 and 80 mg/kg doses were significantly longer than that of 20 mg/kg dose (P < 0.05). The volume of distribution at steady state was similar among the groups (P > 0.05). When compared to 20 mg/kg, dose-normalized AUC(0-infinity) at the 80 mg/kg dose significantly increased (P < 0.05). The relation between dose and AUC(0-infinity) was linear. Our study showed that CTX can be used at 12-h intervals for 20, 40, and 80 mg/kg doses to maintain T > minimum inhibitory concentration (MIC) of > 40% for the treatment of infections caused by bacteria with MIC values <= 2, <= 4, and <= 16 mu g/mL, respectively. This information may be helpful in adjusting the dosage regimen, but there is a need for future work.Öğe Pharmacokinetics of enrofloxacin and danofloxacin in premature calves(Wiley, 2019) Corum, Orhan; Altan, Feray; Yildiz, Ramazan; Ider, Merve; Ok, Mahmut; Uney, KamilThe aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC(0-48)) 139.75 and 38.90 hr*mu g/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr(-1) kg(-1), respectively. The PK parameters of ENR and DNX following IM injection were t(1/2 lambda z) 21.10 and 28.41 hr, AUC(0-48) 164.34 and 48.32 hr*mu g/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC(0-48CPR)/AUC(0-48ENR) ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC(0-24)/minimum inhibitory concentration (MIC) and maximum concentration (C-max)/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 mu g/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.Öğe Pharmacokinetics of levamisole in the red-eared slider turtles (Trachemys scripta elegans)(Wiley, 2019) Corum, Orhan; Durna Corum, Duygu; Atik, Orkun; Altan, Feray; Er, Ayse; Uney, KamilThe pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr(-1) kg(-1) and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 mu g/ml, respectively, with 0.5 hr of T-max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t(1/2z), can be recommended as an effective way for treating nematodes in turtles.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, KamilThe 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.
