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ASSESSMENT OF THE CARDIOTOXICITY OF TULATHROMYCIN IN RABBITS
(AKADEMIAI KIADO ZRT, 2011) Er, Ayse; Altan, Feray; Cetin, Gul; Dik, Burak; Elmas, Muammer; Yazar, Enver
The aim of this study was to determine the cardiotoxic potency of tulathromycin. Tulathromycin (10 mg/kg, SC) was administered to ten adult male rabbits, and blood samples were obtained before and after drug administration (0 and 6 hours). Serum cardiac damage markers (troponin I, creatine kinase-MB, myoglobin, lactate dehydrogenase, aspartate aminotransferase), routine serum biochemical values (alkaline phosphatase, alanine aminotransferase, gammaglutamyltransferase, creatinine, blood urea nitrogen, cholesterol, triglyceride, high-density lipoprotein, amylase, total protein, albumin, glucose, calcium, ionised calcium, sodium, potassium), white blood cell (WBC) and red blood cell (RBC) counts, arterial blood gas parameters (pH, partial carbon dioxide pressure, partial oxygen pressure, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, base excess in vitro, oxygen saturation, packed cell volume, haemoglobin) and serum oxidative status (malondialdehyde, nitric oxide, superoxide dismutase, retinol, beta-carotene) were measured. Increased levels of troponin I, creatine kinase-MB and creatinine, and decreased WBC counts, ionised calcium and potassium levels were observed after drug administration. Tulathromycin treatment may cause cardiotoxicity, but its effects may be less dramatic than those of other macrolide antibiotics frequently used in veterinary medicine.
Determination of the Efficiencies of the Prokinetics in Ruminants with Postoperative Ileus Using Pro-Inflammatory Markers
(UNIV FED RIO GRANDE DO SUL, 2018) Altan, Semih; Donmez, Kaan; Altan, Feray; Alkan, Fahrettin
Background: Recently, the role of inflammation triggered by handling of the intestine various gastrointestinal (GI) surgeries is generally accepted as the key event in postoperative ileus (POI). Because, prokinetics have been increased the smooth muscle contractions and may act by attenuating the inflammatory process in the GI tract, they have been used the treatment of POI in human and animals. There are many in vivo analysis techniques of GI motility. However, there have not yet been studied associated with the evaluation of the inflammatory response. Therefore, it was aimed to evaluate the efficiencies of 3 different prokinetics from inflammatory response during experimentally-induced POI. Materials, Methods & Results: Twenty healthy lambs (30-45 days old) were randomly assigned to four groups. In all groups, enterotomy was performed on the ileum. Erythromycin and metoclopramide were administered to the ERT and MET groups before the surgery, respectively, while lidocaine was administered to the LID group as bolus before and continuous rate infusion during the surgery. Physiological saline was administered to the lambs in control group as placebo before the surgery. Blood samples were collected before surgery (similar to 30-45 min), at the end of surgery (0 h), and at the postoperative 1, 3, 5, 10, 48, 72 and 96 h. The concentrations of serum amyloid A (SAA), haptoglobin (HPT), fibrinogen (FIB) as acute phase proteins (APPs), thiobarbituric acide reactant substrate (TBARs), myeloperoxidase (MPO) as reactive oxygen species, and transforming growth factor-beta (TGF-beta) as a cytokine were measured with ELISA reader. In terms of time points, it was found that FIB was statistically higher in ERT group at the 1st h, in MET and LID groups at the 10th h, and in LID group at the 48th and in MET group at the 72 h (P < 0.05). It was found that SAA was higher in MET group at the 1st, 3rd, 5th, 10th, 24th, 48th and 72nd h. HPT was higher in CNTR group until 72th h and MET group at 48th, 72nd and 96th h. TBARs concentrations were statistically higher in MET and LID groups at 0 hour, in ERT and MET groups at the 1st h, in MET group at the 3rd h, in MET and LID groups at the 5th and 10th h, in MET group at the 48th, 72nd and 96th h (P < 0.05). MPO concentrations was higher in LID group at the 3rd, 5th, 10th and 96th h, and in ERT group at the 72nd h (P < 0.05). TGF-beta concentrations were particularly high in MET group at the 3rd, 5th, 48th and 72nd h, and in LID group at the 10th, 24th, and 96th h (P < 0.05). Discussion: APPs (HPT, SAA, FIB), which are important regulators of inflammation in cows and sheep, were higher generally in MET and LID groups and inflammation persists in these two groups and, therefore, metoclopramide and lidocaine are less effective in early postoperative POI treatment. Because, significant increase in serum TBARs and MPO concentrations was considered as an important indicator of oxidative stress and inflammatory response MPO concentrations was particularly high until 10th h in LID group, and TBARs concentrations was high both MET and LID groups throughout the study, this was correlated with higher neutrophil infiltration in the postoperative early period than the other groups. It is known that TGF-beta, an inflammatory cytokine, is correlated with various smooth muscle disorders in humans. In this study, TGF-beta concentration were higher in the MET and LID groups. High concentration of this cytokine might have led to decrease contractions in smooth muscles, thereby slowing down the intestinal transition. In conclusion, based on the presence of pro-inflammatory markers in this study, erythromycin seems to be the most suitable prokinetic drug in lambs. Moreover, lidocaine and metoclopramide are not as successful in small ruminants as reported in other species.
Development and Validation of a High-Performance Liquid Chromatography Method for Determination of Cefquinome Concentrations in Sheep Plasma and Its Application to Pharmacokinetic Studies
(AMER SOC MICROBIOLOGY, 2011) Uney, Kamil; Altan, Feray; Elmas, Muammer
Cefquinome has a broad spectrum of antibacterial activity and was developed especially for use in animals. A simple and sensitive high-performance liquid chromatography (HPLC) method with UV-visible detection for quantification of cefquinome concentrations in sheep plasma was developed and validated. Separation of cefquinome from plasma components was achieved on a Phenomenex Gemini C-18 column (250 mm by 4.6 mm; internal diameter [i.d.], 5 mu m). The mobile phase consisted of acetonitrile and 0.1% trifluoroacetic acid in water and was delivered at a rate of 0.9 ml/min. A simple and rapid sample preparation involved the addition of methanol to 200 mu l of plasma to precipitate plasma proteins followed by direct injection of 50 mu l of supernatant into the high-performance liquid chromatography system. The linearity range of the proposed method was 0.02 to 12 mu g/ml. The intraday and interday coefficients of variation obtained from cefquinome were less than 5%, and biases ranged from -3.76% to 1.24%. Mean recovery based on low-, medium-, and high-quality control standards ranged between 92.0 and 93.9%. Plasma samples were found to be stable in various storage conditions (freeze-thaw, postpreparative, short-term, and long-term stability). The method described was found to be readily available, practicable, cheap, rapid, sensitive, precise, and accurate. It was successfully applied to the study of the pharmacokinetics of cefquinome in sheep. This method can be very useful and an alternate to performing pharmacokinetic studies in the determination of cefquinome for clinical use.
Effect of etanercept on cytokines and 13, 14-dihydro-15-keto-prostaglandin F2 alpha concentrations during endotoxemia
(WILEY-BLACKWELL, 2012) Er, Ayşe; Dik, Burak; Altan, Feray; Çetin, Gül; Üney, Kamil; Elmas, Muammer; Yazar, Enver
[Abstract not Available]
Effect of Multiple-Dose Administration of Cefquinome on Hematological and Biochemical Parameters in Horse
(2019) Altan, Feray; Erol, Hanifi; Altan, Semih; Arıcan, Mustafa; Elmas, Muammer; Üney, Kamil
The negative impact of multiple ascending doses of cefquinome (CFQ) on hematological and serum biochemical profile of horseunknown. The objective of this study was to evaluate the effect of multiple ascending doses of cefquinome (CFQ) in horses on thefollowing hematological (WBCs, LYM, MON, GRA, RBCs, HB, HT, MCV, MCH, MCHC, RDW, and PLT) and biochemical parameters (ALB,ALP, ALT, AST, CH, CR, GGT, LDH, TB, TP, TRIG, and BUN). The study was performed on the sixteen mature horses (4.6 2.1 years, 302 38 kg). Four dosages of CFQ were applied as Group I; 1 mg/kg, Group II; 2 mg/kg, Group III; 4 mg/kg and Group IV; 6 mg/kg, and eachanimal received intravenously a total of 13 injections, administered every 12 h for 7 days. The hematological and biochemicalparameters of horses were monitored on the before 0 day and 1, 3, 7, and 14 days after the administration of the first CFQ. Nosignificant differences in serum biochemical parameters were found amongst the groups (p0.05). Significant differences were found incertain hematological parameters (MONO, GRAN, RBC, HB, HCT, MCH, and PCT) amongst the groups (p0.05) within the referenceranges. These results indicate that the administration of multiple doses of up to 6 mg/kg of CFQ in the horse had no clinically significantimpact on the blood parameters measured.
EFFECTS OF DIFFERENT DOSES OF DEXAMETHASONE PLUS FLUNIXIN MEGLUMINE ON SURVIVAL RATE IN LETHAL ENDOTOXEMIA
(DE GRUYTER POLAND SP ZOO, 2009) Er, Ayşe; Üney, Kamil; Altan, Feray; Çetin, Gül; Yazar, Enver; Elmas, Muammer
Effects of different doses of dexamethasone plus flunixin meglumine on survival rate were investigated in lethal endotoxemia. A total of 60 Balb/C female mice were divided into 4 equal groups. Lethal endotoxemia (80-100%) was induced by lipopolysaccharide injection (Group 1, 1 mg, intraperinoneally). At 4 hours after the lipopolysaccharide injection; low-dose dexamethasone (0.6 mg/kg, SID, 5 days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days, subcutaneously), normal-dose dexamethasone (2 mg/kg, SID, 5 days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days, subcutaneously) and high-dose dexamethasone (10 mg/kg, SID, 5 days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days, subcutaneously) were injected to Group 2, 3 and 4, respectively. After the injections, survival was monitored at 7 days and 13.3%, 13.3%, 33.3% and 73.3% survival rates were observed in Groups 1, 2, 3 and 4, respectively. As results, high-dose dexamethasone plus flunixin meglumine may be the treatment of choice for endotoxaemia in animals.
Effects of drugs on kinetic values of cytokines, adenosine deaminase and 13,14-dihydro-15-keto-prostaglandin F2? in endotoxemia: A different approach
(Selçuk Üniversitesi Veterinerlik Fakültesi, 2010) Altan, Feray; Çetin, Gül
Amaç: Lipopolisakkaritle (LPS) oluşturulan deneysel endotoksemide sitokinler, adenozin deaminaz (ADA) ve 13,14-dihidro-15-keto-prostaglandin F2? (PGM)’nın kinetik değerlerine tek başlarına ve/veya kombine uygulanan enrofloksasin (ENR), fluniksin meglumin (FM) ve deksametazonun (DEX) etkilerini belirlemektir. Gereç ve Yöntem: Araştırmada kullanılan ratlar 7 gruba ayrıldı. Deneysel endotoksemi oluşturmak için pozitif kontrol grubu dahil bütün gruplara LPS uygulandı. Diğer altı gruba ENR, FM, düşük doz DEX, yüksek doz DEX, ENR+FM+düşük doz DEX ve ENR+FM+yüksek doz DEX uygulandı. Uygulama sonrası 0, 1, 2, 4, 6, 8, 12, 24 ve 48. saatlerde kan örnekleri toplandı. Tümör nekroz faktör alfa (TNF?), interlökin-6 (IL6), interlökin-10 (IL-10), ADA ve PGM düzeyleri ELISA ile belirlendi. Eğri altında kalan alan (EAA0-48) farmakokinetik programla, plazma veya serum maksimum konsantrasyon (Cmax) ile maksimum konsantrasyona ulaşma zamanı (tmax) direk bakı yöntemiyle belirlendi. Bulgular: Pozitif kontrol (LPS) grubuyla kıyaslandığında EAA0-48 değerlerinin; ENR grubunda PGM için artarken (p<0.05), IL-6, IL-10 ve ADA için azaldığı (p<0.05); FM grubunda IL-6 ve ADA’ya özgü olarak küçüldüğü (p<0.05); DEX tek başına veya kombine uygulandığı gruplarda da azaldığı (p<0.05) belirlendi. Öneri: Farklı örnekleme zamanlarında çok sayıda ölçülen aynı endotoksemi belirteçlerinin toplu değerlendirilmesinde kinetik parametrelerden özellikle EAA’nin farklı ve akılcı bir yaklaşım olarak dikkate alınabileceği kanaatine varıldı
Effects of Drugs on Kinetic Values of Cytokines, Adenosine Deaminase and 13,14-dihydro-15-keto-prostaglandin F? in Endotoxemia: A Different Approach 2
(2010) Altan, Feray; Elmas, Muammer; Er, Ayşe; Üney, Kamil; Çetin, Gül; Traş, Bünyamin; Yazar, Enver
Amaç: Lipopolisakkaritle (LPS) oluşturulan deneysel endotoksemide sitokinler, adenozin deaminaz (ADA) ve 13,14-dihidro-15-keto-prostaglandin F2? (PGM)’nın kinetik değerlerine tek başlarına ve/veya kombine uygulanan enrofloksasin (ENR), fluniksin meglumin (FM) ve deksametazonun (DEX) etkilerini belirlemektir. Gereç ve Yöntem: Araştırmada kullanılan ratlar 7 gruba ayrıldı. Deneysel endotoksemi oluşturmak için pozitif kontrol grubu dahil bütün gruplara LPS uygulandı. Diğer altı gruba ENR, FM, düşük doz DEX, yüksek doz DEX, ENR+FM+düşük doz DEX ve ENR+FM+yüksek doz DEX uygulandı. Uygulama sonrası 0, 1, 2, 4, 6, 8, 12, 24 ve 48. saatlerde kan örnekleri toplandı. Tümör nekroz faktör alfa (TNF?), interlökin-6 (IL6), interlökin-10 (IL-10), ADA ve PGM düzeyleri ELISA ile belirlendi. Eğri altında kalan alan (EAA0-48) farmakokinetik programla, plazma veya serum maksimum konsantrasyon (Cmax) ile maksimum konsantrasyona ulaşma zamanı (tmax) direk bakı yöntemiyle belirlendi. Bulgular: Pozitif kontrol (LPS) grubuyla kıyaslandığında EAA0-48 değerlerinin; ENR grubunda PGM için artarken (p<0.05), IL-6, IL-10 ve ADA için azaldığı (p<0.05); FM grubunda IL-6 ve ADA’ya özgü olarak küçüldüğü (p<0.05); DEX tek başına veya kombine uygulandığı gruplarda da azaldığı (p<0.05) belirlendi. Öneri: Farklı örnekleme zamanlarında çok sayıda ölçülen aynı endotoksemi belirteçlerinin toplu değerlendirilmesinde kinetik parametrelerden özellikle EAA’nin farklı ve akılcı bir yaklaşım olarak dikkate alınabileceği kanaatine varıldı.
Effects of Enrofloxacin, Flunixin and Dexamethasone on Indicators of Oxidative and Organ Damage in Lipopolysaccharide-Induced Endotoxemia
(Medwell Online, 2010) Er, Ayşe; Altan, Feray; Çetin, Gül; Üney, Kamil; Traş, Bünyamin; Elmas, Muammer; Yazar, Enver
The aim of this study was to determine the effects of enrofloxacin., flunixin meglumine and dexamethasone on antioxidant status and markers of organ damage in endotoxemia. Rats were divided into four groups. The groups received the following drugs (simultaneously with lipopolysaccharide): enrofloxacin, flunixin meglumine, low-dose dexamethasone or high-dose dexamethasone, respectively. After the treatments, serum and plasma samples were collected at 1, 2, 4, 6, 8, 12, 24 and 48 h. The levels of malondialdehyde, nitric oxide, superoxide dismutase, vitamin C and 13,14-dihydro-15-keto-prostaglandin F-2 alpha were determined with ELISA. The cardiac, hepatic and renal damage markers were measured with autoanalyzer. Elevated levels of malondialdehyde were relatively inhibited by high-dose dexamethasone. Increases in the levels of nitric oxide were inhibited by low and high-dose dexamethasone while increases in the level of 13,14-dihydro-15-keto prostaglandin F-2 alpha were inhibited by all treatments except enrofloxacin. No treatments inhibited the decrease in vitamin C levels. Cardiac and hepatic damage was not inhibited completely whereas renal damage was inhibited by treatment with low or high-dose dexamethasone. The results show that although low-dose dexamethasone had antioxidant activity and protected against organ damage, high-dose dexamethasone may be more beneficial in the treatment of endotoxemia.
The effects of Mannheimia haemolytica and albendazole on marbofloxacin pharmacokinetics in lambs
(SPRINGER, 2019) Altan, Feray; İpek, Duygu Neval Sayın; Çorum, Orhan; Alp, Simten Yeşilmen; İpek, Polat; Üney, Kamil
The 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.
The effects of three different prokinetic drugs on the motility hormones level in lambs with postoperative ileus
(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2018) Altan, Semih; Donmez, Kaan; Altan, Feray; Alkan, Fahrettin
The aim of this study was to evaluate the effects of the three different prokinetic agents, namely erythromycin, lidocaine, and metoclopramide in lambs with postoperative ileus (POI) using motilin and ghrelin, which are known as motility markers. Twenty lambs were allocated to 4 groups of 5 lambs each. An enterotomy was performed on the ileum of each lamb. Erythromycin (8.8 mg/ kg), metoclopramide (0.2 mg/kg), and saline (2 mL) were administered as single dose IM before surgery in the ERT, MET, and CNTR groups, respectively. Lidocaine was administered to the LID group, both as a bolus before (1.3 mg/kg IV) and as a continuous rate infusion during surgery (0.05 mg/kg/h IV). Serwn motilin and ghrelin concentrations as motility hormones were measured with ELISA. The serum motilin concentration was significantly higher at 0, 1, 3, 5, 10, 24, and 48 h in the ERT group and at 1 and 10 h in the LID group. The serum ghrelin concentration was significantly higher at 0, 1, and 48 h in the ERT group and at 3, 5, 10, 24, and 48 h in the LID group. As a result, erythromycin and lidocaine was thought to be useful in lambs with POI according to the stimulatory effects on the motility hormones.
Effects of Tylosin on Serum Cytokine Levels in Healthy and Lipopolysaccharide-Treated Mice
(Akademiai Kiado Zrt, 2010) Er, Ayşe; Yazar, Enver; Üney, Kamil; Elmas, Muammer; Altan, Feray; Çetin, Gül
The effects of different doses of tylosin on serum cytokine concentrations were investigated in healthy and lipopolysaccharide-treated mice. The mice were divided into seven groups. Lipopolysaccharide (LPS) was injected into the positive control group. The other six groups received three different tylosin doses concurrently without or with LPS: 10 mg/kg, 100 mg/kg, 500 mg/kg, 10 mg/kg + LPS, 100 mg/kg + LPS and 500 mg/kg + LPS. After treatment, serum samples were collected at 0, 1, 2, 3, 6, 12 and 24 hours. Serum tumour necrosis factor alpha (TNF alpha), interleukin 1 beta (IL1 beta) and IL10 levels were determined by enzyme-linked immunosorbent assay (ELISA). Tylosin doses of 10 and 100 mg/kg induced no cytokine production in the healthy mice. Tylosin at 500 mg/kg had no effect on TNF alpha or IL1 beta production, but it induced IL10 production in healthy mice. All doses of tylosin reduced the elevated TNF alpha and IL1 beta in LPS-treated mice but increased their IL10 levels. In conclusion, these data suggest that tylosin has an immunomodulatory effect at the dose recommended for use against infection.
Etanersept - endotoksemi tedavisinde kullanılabilir mi?
(2013) Er, Ayse; Dık, Burak; Cetın, Gul; Altan, Feray; Uney, Kamil; Elmas, Muammer; Yazar, Enver
Araştırmanın amacı endotoksemide etanersept uygulamasının kan sitokinler, fibrinojen, antitrombin, 13,14-dihidro-15-keto prostaglandin F2? ve biyokimyasal parametrelere etkisini araştırmaktır. Erişkin 126 adet Sprague Dawley ırkı erkek rat 3 gruba ayrılarak; 1. Gruba lipopolisakkarit (4 mg, IP), 2. Gruba etanersept (8 mg/kg, IP) ve 3. Gruba lipopolisakkarit etanersept uygulamaları yapıldı. Uygulamalardan sonra 0., 1., 2., 4., 8., 12. ve 24. saatlerde kan örnekleri alındı. Serum tümör nekrozis faktör-?, interlöykin-1?, interlöykin-10 ve plazma 13,14-dihidro-15-keto-prostaglandin F2? düzeyleri ELISA okuyucusunda; sitratlı plazma antitrombin ve fibrinojen düzeyleri koagulometrede; serum biyokimyasal parametreleri otoanalizörde belirlendi. Etanerseptin fibrinojen düzeyinde düzensiz değişimlere ve 13,14-dihidro-15-keto-prostaglandin F2?, alkalen fosfataz ile alanin aminotransferaz düzeyinde yükselmelere neden olduğu belirlendi. Lipopolisakkarit uygulaması sitokinler, 13,14-dihidro-15-keto-prostaglandin F2?, fibrinojen, organ hasar belirteçleri ve trigliserit düzeylerinde yükselmelere neden olurken, antitrombin seviyesinde düzensiz değişimlere neden oldu. Lipopolisakkarit etanersept uygulanan grupta sitokinler, 13,14-dihidro-15-keto-prostaglandin F2? ve fibrinojen düzeyinde yükselmeler, antirombin düzeyinde düzensiz değişimler gözlendi. Lipopolisakkarit uygulaması ile yükselen kreatin kinaz-MB düzeyinin etanersept tarafından tamamen, tümör nekrozis faktör-? yükselmesinin kısmen engellendiği ancak kanda kalış süresini uzattığı ve interlöykin-10 düzeyini daha fazla yükselttiği belirlendi. Sonuç olarak endotoksemide etanerseptin kalp üzerindeki koruyucu etkisi ve interlöykin-10 düzeyini yükseltmesi nedeni ile tek doz uygulamasının veteriner sahada faydalı olabileceği belirlendi.
Farklı dozlardaki marbofloksasinin koyunlarda biyokimyasal ve hematolojik parametreler üzerine etkileri
(Selçuk Üniversitesi Veterinerlik Fakültesi, 2018) Altan, Feray; Çorum,Orhan; Çorum,Duygu Durna
Amaç: Mevcut araştırmada sağlıklı koyunlarda kas içi farklı dozlarda marbofloksasin uygulamasının biyokimyasal ve hematolojik parametreler üzerine etkisinin belirlenmesi amaçlandı. Gereç ve Yöntem: Çalışma, paralel dizayna göre dört doz grubunda ayrılan 24 adet sağlıklı erkek, 2-5 yaştaki Akkaraman koç üzerinde gerçekleştirildi. Herbir doz grubunda 6 adet hayvan bulunmaktadır. Her gruptaki altı hayvana, semitendinoz kas bölgesinden sırasıyla 2, 4, 6 ve 10 mg/kg tek doz seviyelerinde marbofloksasin enjekte edildi. Kan örnekleri sol vena jugularise yerleştirilen kataterler kullanılarak ilaç uygulanmadan önce (0.saat, kontrol) ve sonraki 10. ve 22. saatlerde alındı. Biyokimyasal parametrelerden albumin, alkalin fosfataz, alanin aminotransferaz, aspartat aminotransferaz, kolesterol, trigliserid, total protein, kan üre nitrojen, kreatinin ve gamma-glutamil transferaz değerleri otoanalizör cihazında belirlendi. Hematolojik parametrelerden beyaz kan hücreleri, kırmızı kan hücreleri, hemoglobin, hematokrit, platelet değerleri kan hücresi sayım cihazında ölçüldü. Bulgular: Gruplar arasında hematolojik ve serum biyokimyasal parametrelerinde anlamlı bir fark bulunamadı. Öneri: Bu sonuçlar koyunlarda tek doz kas içi uygulanmasından sonra 10 mg/kg'a kadar tek bir intramüsküler enjeksiyondan sonra marbofloksasinin hematolojik ve biyokimyasal parametreler üzerinde klinik olarak anlamlı bir etkisinin olmadığını göstermektedir.
Farklı dozlardaki marbofloksasinin koyunlarda biyokimyasal ve hematolojik parametreler üzerine etkileri
(2018) Altan, Feray; Çorum, Orhan; Çorum, Duygu Durna; Üney, Kamil
Amaç: Mevcut araştırmada sağlıklı koyunlarda kas içi farklıdozlarda marbofloksasin uygulamasının biyokimyasal ve hematolojikparametreler üzerine etkisinin belirlenmesi amaçlandı.Gereç ve Yöntem: Çalışma, paralel dizayna göre dört doz grubundaayrılan 24 adet sağlıklı erkek, 2-5 yaştaki Akkaramankoç üzerinde gerçekleştirildi. Herbir doz grubunda 6 adet hayvanbulunmaktadır. Her gruptaki altı hayvana, semitendinoz kasbölgesinden sırasıyla 2, 4, 6 ve 10 mg/kg tek doz seviyelerindemarbofloksasin enjekte edildi. Kan örnekleri sol vena jugulariseyerleştirilen kataterler kullanılarak ilaç uygulanmadan önce(0.saat, kontrol) ve sonraki 10. ve 22. saatlerde alındı. Biyokimyasalparametrelerden albumin, alkalin fosfataz, alanin aminotransferaz,aspartat aminotransferaz, kolesterol, trigliserid, totalprotein, kan üre nitrojen, kreatinin ve gamma-glutamil transferazdeğerleri otoanalizör cihazında belirlendi. Hematolojikparametrelerden beyaz kan hücreleri, kırmızı kan hücreleri,hemoglobin, hematokrit, platelet değerleri kan hücresi sayımcihazında ölçüldü.Bulgular: Gruplar arasında hematolojik ve serum biyokimyasalparametrelerinde anlamlı bir fark bulunamadı.Öneri: Bu sonuçlar koyunlarda tek doz kas içi uygulanmasındansonra 10 mg/kg'a kadar tek bir intramüsküler enjeksiyondansonra marbofloksasinin hematolojik ve biyokimyasal parametrelerüzerinde klinik olarak anlamlı bir etkisinin olmadığınıgöstermektedir.
Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep
(WILEY, 2019) Altan, Feray; Corum, Orhan; Yildiz, Ramazan; Faki, Hatice Eser; Ider, Merve; Ok, Mahmut; Uney, Kamil
In 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.
Pharmacokinetic Profile of Ceftiofur Sodium in Endotoxemic Newborn Calves Treated with Single and Combined Therapy
(WILEY-BLACKWELL, 2012) Elmas, Muammer; Altan, Feray; Üney, Kamil; Er, Ayşe; Yazar, Enver
[Abstract not Available]
Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves
(WILEY, 2019) Çorum, Orhan; Yıldız, Ramazan; İder, Merve; Altan, Feray; Ok, Mahmut; Üney, Kamil
The 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.
Pharmacokinetics and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous, intramuscular, subcutaneous, and oral administrations
(WILEY, 2019) Çorum, Orhan; Çorum, Duygu Durna; Atik, Orkun; Fakı, Hatice Eser; Altan, Feray; Üney, 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.
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, Kamil
In 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.

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