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Aflatoksin b1'in fare beynine geçişi üzerine bcrp ve p-gp modülatörlerinin etkisi
(2017) Tras, Bunyamin; Cetın, Gul; Uney, Kamil; Dık, Burak; Corum, Orhan; Atalay, Sema
Çalışma, zosuquidar ve prazosin tarafından sırasıyla P-gp ve BCRP modülasyonunun AFB1'in plazma ve beyin konsantrasyonlarının etkileyip etkilemediğini belirlemek için gerçekleştirildi. Bu çalışmada, 40 adet sağlıklı, erkek BALB/c ırkı fare (323.7 g) kullanıldı. Hayvanlar her grupta 8 fare olacak şekilde rastgele 5 gruba ayrıldı. Grup 1, metod validasyon çalışmalarında kullanıldı. Grup 2 (AF)'ye AFB1 20 mg/kg dozda intraperitoneal yolla verildi. Grup 3 (AFPRZ), 4 (AFZQR) ve 5 (AFPRZZQR)'e ise sırasıyla intraperitoneal yolla prazosin (0.3 mg/kg), zosuquidar (25 mg/kg) ve prazosinzosuquidar (0.3 mg/kg prazosin 25 mg/kg zosuquidar) uygulamalarından 30 dk. sonra AFB1 20 mg/kg dozda intraperitoneal yolla uygulandı. Grup 2-5'de bulunan hayvanlardan AFB1 uygulamasından sonraki 6. saatte kan ve beyin örnekleri alındı. AFB1 düzeyleri fluoresans dedektör içeren HPLC sisteminde tayin edildi. Prazosin ve zosuquidarın tek ve eşzamanlı uygulanması AFB1'in beyin konsantrasyonlarında sadece AFB1uygulamasına göre önemli oranda azalmaya neden oldu (P0.05). AFB1 grubunda AFB1'in beyin/plazma oranı diğer gruplardan (AFPRZ, AFZQR, and AFPRZZQR) önemli oranda daha yüksekti (P0.05). Akut AFB1 zehirlenmelerinde özellikle BCRP gibi transmembran proteinlerin indüklenmesi hayatta kalma oranını artırabilir.
Comparative Pharmacokinetics and Metabolisms of Caffeine in Sheep Breeds
(JAPAN SOC VET SCI, 2011) Uney, Kamil; Tras, Bunyamin
The purpose of this study was to investigate the effect of breed on the pharmacokinetics and metabolism of caffeine (CF) and the hepatic metabolic capacity in sheep. CF was administered as a single intravenous dose of 5 mg/kg b.w. in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds. The plasma levels of CF and its primary metabolites, theobromine (TB), paraxanthine (PX) and theophylline (TP), were measured using high-performance liquid chromatography. Pharmacokinetic parameters of CF and its metabolites were calculated. Plasma TB+PX+TP/CF metabolic ratio was determined as an alternative to CF clearance for the determination of hepatic metabolic capacity. In the three breeds, all kinetic parameters of CF differed significantly (P<0.05) except for volume of distribution. Elimination of CF was slow in the MK (Cl(T); 0.03 +/- 0.01 l hr/kg, t(1/2 lambda z); 15.74 +/- 7.35 hr) and AM (Cl(T); 0.05 +/- 0.02 / hr/kg, t(1/2 lambda z); 9.68 +/- 5.21 hr) breeds when compared with the AK breed (Cl(T); 0.08 +/- 0.01 l hr/kg, t(1/2 lambda z), 6.84 +/- 0.79 hr). There was significant correlation (r(2)=0.904, P<0.01) between CF clearance and the plasma TB+PX+TP/CF ratio calculated at 7 hr after CF administration. The plasma TB+PX+TP/CF ratios were statistically different (P<0.05) among the breeds (MK, 0.155 +/- 0.062; AK, 0.468 +/- 0.107; AM, 0.254 +/- 0.099). These results suggest that the pattern of drug biotransformation should be consistently tested for all breeds within species. Further studies are needed to determine the biochemical and molecular events underlying such an effect.
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 Nerium oleander distillate on MCF-7 breast cancer cell lines
(CURRENT BIOLOGY LTD, 2011) Kars, Meltem Demirel; Kars, Gokhan; Gunduz, Ufuk; Uney, Kamil; Bas, Ahmet Levent
[Abstract not Available]
Effect of Tilmicosin on Serum Cytokine Levels in the Endotoxemia
(2009) Uney, Kamil; Er, Ayşe; Avcı, Gülcan; Bülbül, Aziz; Elmas, Muammer; Yazar, Enver
Abstract: The effect of tilmicosin on serum cytokine concentrations were investigated in healthy and lipopolysaccharide-treated mice. The mice were divided into 3 groups. Lipopolysaccharide (250 µg, Escherichia coli 0111:B4, intraperitoneally) was injected into the positive control group. The other 2 groups received tilmicosin (20 mg kg, subcutaneously) concurrently without or with lipopolysaccharide. After treatment, serum samples were collected at 0, 1.5, 3, 6, 12 and 24 h. Serum tumor necrosis factor, interleukin-1 and interleukin-10 levels were determined by enzyme-linked immunosorbent assay. Lipopolysaccharide increased all cytokine levels in the healthy mice. Tilmicosin slightly induced interleukin-1 production in the healthy mice, while it had no effect on tumor necrosis factor or interleukin-10 productions. However, tilmicosin elevated (p<0.05) tumor necrosis factor, interleukin-1 and interleukin-10 levels in lipopolysaccharide-treated mice. In conclusion, these data suggest that tilmicosin stimulates both proinflammatory and antiinflammatory cytokines at the dose recommended for infection.
Effect of Tilmicosin on Serum Cytokine Levels in the Endotoxemia
(MEDWELL ONLINE, 2009) Uney, Kamil; Er, Ayse; Avci, Gulcan Erbil; Bulbul, Aziz; Elmas, Muammer; Yazar, Enver
The effect of tilmicosin on serum cytokine concentrations were investigated in healthy and lipopolysaccharide-treated mice. The mice were divided into 3 groups. Lipopolysaccharide (250 mu g, Escherichia coli 0111:B4, intraperitoneally) was injected into the positive control group. The other 2 groups received tilmicosin (20 mg kg(-1), subcutaneously) concurrently without or with lipopolysaccharide. After treatment, serum samples were collected at 0, 1.5, 3, 6, 12 and 24 h. Serum tumor necrosis factor, interleukin-1 and interleukin-10 levels were determined by enzyme-linked immunosorbent assay. Lipopolysaccharide increased all cytokine levels in the healthy mice. Tilmicosin slightly induced interleukin-1 production in the healthy mice, while it had no effect on tumor necrosis factor or interleukin-10 productions. However, tilmicosin elevated (p<0.05) tumor necrosis factor, interleukin-1 and interleukin-10 levels in lipopolysaccharide-treated mice. In conclusion, these data suggest that tilmicosin stimulates both proinflammatory and antiinflammatory cytokines at the dose recommended for infection.
Effects of bcrp and p-gp modulators on the penetration of aflatoxin b1 into the mouse brain
(KAFKAS UNIV, VETERINER FAKULTESI DERGISI, 2017) Tras, Bunyamin; Cetin, Gul; Uney, Kamil; Dik, Burak; Corum, Orhan; Atalay, Sema
This study was conducted to determine whether the plasma and brain concentrations of AFB(1) are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32 +/- 3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1 at a dose of 20 mg/kg of body weight. Groups 3 (AF+PRZ), 4 (AF+ZQR), and 5 (AF+PRZ+ZQR) received 20 mg/kg of AFB(1) intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosin+zosuquidar (0.3 mg/kg prazosin + 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB(1), blood and brain samples were collected from the animals in Groups 2 to 5. AFB(1) concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB(1) in comparison to a single administration of AFB(1) (P<0.05). The brain/plasma ratio of the AF group was higher than that of the other groups (AF+PRZ, AF+ZQR, and AF+PRZ+ZQR) (P<0.05). Inducers of transmembrane proteins, especially BCRP, can be life saving during acute AFB(1) poisoning.
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.
Implications from a pharmacogenomic analysis: Nerium oleander leaf distillate supplemented diet regulates cholesterol metabolism in rats
(TAYLOR & FRANCIS LTD, 2014) Kars, Meltem Demirel; Odabasi, Burcu Asena; Kars, Gokhan; Uney, Kamil; Bagci, Yavuz; Bas, Ahmet Levent
Context: Despite the usage of Nerium oleander L. (Apocynaceae) for anticancer studies and traditional remediation, the regulatory effect of N. oleander leaf distillate on cholesterol metabolism is not disclosed sufficiently. Objective: Cholesterol is an important biological molecule and the synthesis rate is regulated by the amount of cholesterol uptake from the diet. The aim of this study was to investigate the regulation of cholesterol metabolism in response to a high-fat diet (HFD) and the effects of N. oleander leaf distillate-supplemented diet (NOHFD) in rats. Materials and methods: Microarray technology was used to clarify the regulation of cholesterol mechanism in HFD and NOHFD-fed rats (375 mu g/0.5 mL distilled water applied by gavage). The treatment period was 90 days. Rat liver tissues were used for microarray analysis using the Affymetrix GeneChip Rat Genome platform. Results of groups were statistically analyzed with the Partek 6.6 bioinformatic program. Results: The HFD group exhibited alterations in the expression levels of about 1945 genes with respect to the normal diet (ND) group. The results showed that expression levels of 47 genes were altered related to cholesterol metabolism in HFD and NOHFD groups. The expression levels of seven genes in the NOHFD group were significantly closer to those in the ND group than those of the HFD group. Discussion and conclusion: To conclude, findings suggest that N. oleander leaf distillate-supplemented food has considerable beneficial effects on cholesterol metabolism-related gene expression levels.
Increased glucose uptake and insulin binding activity of nerium oleander in hepatocytes and adipocytes
(KAFKAS UNIV, VETERINER FAKULTESI DERGISI, 2013) Yazihan, Nuray; Bas, Ahmet Levent; Ermis, Ezgi; Demirci, Sule; Uney, Kamil
Type 2 diabetes mellitus (DM) affects a large population worldwide. DM is often considered as a syndrome of disordered glucose metabolism. Current conventional drug therapies for DM are usually insufficient and medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Nerium Oleander (N.O.) is known to be effective in lowering of postprandial blood glucose in DM patients as a folk remedy. In this study we aimed to evaluate effect of N.O. distillate in glucose uptake activity of hepatocytes and adipocytes. The human hepatoma cells Hep3B and mouse adipocyte 3T3-L1 cells were cultured. Depending on the groups, different concentrations insulin (1, 10, 20 IU/ml) and N.O. (0.1, 1, 10, 50 mu g/ml) were added to medium for 48 h. Cellular toxicity and proliferation were evaluated by LDH secretion levels and MU test. A metabolizable fluorescent derivative of glucose, 2-NBDG and FITC-insulin were used for glucose uptake and insulin binding activity. Insulin increased cellular proliferation and decreased LDH leakage and apoptosis in both cell types. Lower dosages of N.O. has no significant effect on apoptosis and cell number while at the highest dosages minimal cytotoxicity was seen mainly in adipocytes. Main effect of N.O. treatment was increased glucose uptake in Hep3B and 3T3-L1 cells (P<0.001). Our results showed that N.O. may be offered as new approaches to treatment of type 2 diabetes by modulating cellular glucose uptake.
Influences of flunixin and tenoxicam on the pharmacokinetics of florfenicol in lipopolysaccharide-induced endotoxemia
(SCIENTIFIC TECHNICAL RESEARCH COUNCIL TURKEY-TUBITAK, 2015) Koc, Feride; Atila, Alptug; Karakus, Emre; Uney, Kamil
The purpose of this study was to investigate the influences of flunixin (FM) and tenoxicam (TN) on the pharmacokinetics of florfenicol (FF) after coadministration in lipopolysaccharide (LPS)-induced endotoxemic rabbits. Fifteen male rabbits were used in this study. FF (20 mg/kg), FM (2 mg/kg), and TN (1 mg/kg) were coadministered via intravenous injection to the animals. The concentrations of FF were determined by high-performance liquid chromatography with diode-array detection from 0.08 to 12 h in plasma. The plasma concentration-time profile of FF was described using a noncompartmental open model. In this study, terminal half-life, area under the curve, mean residence time, and volume of distribution at steady state were significantly increased, whereas total body clearance was decreased in coadministered groups. In conclusion, FM and TN have effects on the pharmacokinetics of FF in coadministered endotoxemic rabbits. When FF is coadministered with FM and TN, it can be given at a dose of 20 mg/kg b.w. every 8 h for treatment of infections caused by susceptible pathogens with a minimum inhibitory concentration (MIC) of <= 2 mu g/mL or 12 h for treatment of infections caused by susceptible pathogens with MIC of <= 1 mu g/mL in critically ill rabbits. Further studies are necessary to determine variations in dosage regimens.
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.
Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs
(WILEY, 2019) Ozdemir, Zeynep; Faki, Hatice Eser; Uney, Kamil; Tras, Bunyamin
The purpose of this study was to determine the pharmacokinetic interaction between ivermectin (0.4 mg/kg) and praziquantel (10 mg/kg) administered either alone or co-administered to dogs after oral treatment. Twelve healthy cross-bred dogs (weighing 18-21 kg, aged 1-3 years) were allocated randomly into two groups of six dogs (four females, two males) each. In first group, the tablet forms of praziquantel and ivermectin were administered using a crossover design with a 15-day washout period, respectively. Second group received tablet form of ivermectin plus praziquantel. The plasma concentrations of ivermectin and praziquantel were determined by high-performance liquid chromatography using a fluorescence and ultraviolet detector, respectively. The pharmacokinetic parameters of ivermectin following oral alone-administration were as follows: elimination half-life (t(1/2 lambda z)) 110 +/- 11.06 hr, area under the plasma concentration-time curve (AUC(0-infinity)) 7,805 +/- 1,768 hr(.)ng/ml, maximum concentration (C-max) 137 +/- 48.09 ng/ml, and time to reach C-max (T-max) 14.0 +/- 4.90 hr. The pharmacokinetic parameters of praziquantel following oral alone-administration were as follows: t(1/2 lambda z) 7.39 +/- 3.86 hr, AUC(0-infinity) 4,301 +/- 1,253 hr(.)ng/ml, C-max 897 +/- 245 ng/ml, and T-max 5.33 +/- 0.82 hr. The pharmacokinetics of ivermectin and praziquantel were not changed, except T-max of praziquantel in the combined group. In conclusion, the combined formulation of ivermectin and praziquantel can be preferred in the treatment and prevention of diseases caused by susceptible parasites in dogs because no pharmacokinetic interaction was determined between them.
Measurements of caffeine and plasma metabolite/caffeine ratios as a test for hepatic drug-oxidizing capacity in goats
(TAYLOR & FRANCIS LTD, 2011) Uney, Kamil; Tumer, Ilyas; Tras, Bunyamin
The aim of this investigation was to determine the pharmacokinetics and demethylation of caffeine (CF) and the metabolite/CF ratios that correlated best with CF clearance, which were used to evaluate hepatic drug-oxidizing capacity of CF after a single intravenous dose (5 mg/kg) in hair goats (n == 9). Pharmacokinetic parameters of CF and its metabolites, theobromine (TB), paraxanthine (PX) and theophylline (TP), were calculated. The plasma metabolic ratios TB/CF, PX/CF, TP/CF and TB++PX++TP/CF were determined at 6, 8 and 10 h after CF administration to evaluate their hepatic drug-oxidizing capacity. The plasma concentration--time data of CF were fit to a two-compartment model in all animals. The clearance of CF was 0.08 +/-+/- 0.02 L/h/kg, and the volume of distribution was 0.91 +/-+/- 0.16 L/kg. The demethylation fractions of CF to TB, PX and TP were 0.24, 0.37 and 0.39, respectively. Correlations between the metabolic ratios and CF clearance were quite high, except for the PX/CF ratio, particularly at 6 h (r == 0.650--0.750, P < 0.01, 0.05) and 10 h (r == 0.650--0.767, P < 0.01, 0.05). Plasma metabolite/CF ratios, except for the PX/CF ratio, may be useful as an alternative to measurements of CF clearance for the determination of the hepatic drug-oxidizing capacity in goats.
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.
Pharmacokinetics of ceftiofur in healthy and lipopolysaccharide-induced endotoxemic newborn calves treated with single and combined therapy
(JAPAN SOC VET SCI, 2017) Altan, Feray; Uney, Kamil; Er, Ayse; Cetin, Gul; Dik, Burak; Yazar, Enver; Elmas, Muammer
The aim of this research was to compare plasma pharmacokinetics of ceftiofur sodium (CS) in healthy calves, and in calves with experimentally induced endotoxemia. Six calves received CS (2.2 mg/kg, IM) 2 hr after intravenous administration of 0.9% NaCl (Ceft group). After a washout period, the same 6 calves received CS 2 hr after intravenous injection of lipopolysaccharide (LPS+Ceft group). Another group of 6 calves received a combination of drug therapies that included CS 2 hr after administration of 0.9% NaCl (Comb group). A third group of 6 calves received the same combination therapy regimen 2 hr after intravenous injection of lipopolysaccharide (LPS+Comb group). Plasma concentrations of CS and all desfuroylceftiofurrelated metabolites were determined using HPLC, and its pharmacokinetic properties were determined based on a two-compartment model. The peak concentration of CS in the LPS+Comb group occurred the earliest, and the clearance rate of CS was the highest in the Comb and LPS+ Comb groups (P < 0.05). The elimination half-life of CS in the LPS+Ceft group was longer than that in the Ceft and Comb groups (P < 0.05). The results of this study indicate that combined therapies and endotoxemic status may alter the plasma pharmacokinetics of CS in calves.
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, Kamil
The 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.
Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits
(ELSEVIER SCI LTD, 2008) Elmas, Muammer; Yazar, Enver; Uney, Kamil; Er (Karabacak), Ayse; Tras, Buenyamin
The purpose of this study was to determine the pharmacokinetics and possible interactions of enrofloxacin (ENR) and flunixin meglumine (FM) in healthy rabbits and in rabbits where endotoxaemia had been induced by administering Escherichia coli lipopolysaccharide (LPS). Six male adult New Zealand White rabbits were used for the study. In Phase I, FM (2.2 mg/kg) and ENR (5 mg/kg) were given simultaneously as a bolus intravenous (IV) injection to each healthy rabbit. After a washout period, Phase II consisted of purified LPS administered as an IV bolus injection, then FM and ENR. LPS produced statistically significant increases in some serum biochemical concentrations. After the drugs were co-administered, the kinetic parameters of FM were not significantly different in healthy compared to endotoxaemic rabbits. It is concluded that ENR and FM could be co-administered to rabbits to treat endotoxaemia as no negative interaction was observed between the pharmacokinetics of both drugs. (c) 2007 Elsevier Ltd. All rights reserved.
Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Angora rabbits
(ELSEVIER SCI LTD, 2007) Elmas, Muammer; Uney, Kamil; Yazar, Enver; Karabacak, Ayse; Tras, Bunyamin
The pharmacokinetic behaviour and bioavailability of enrofloxacin (ENR) were determined after single intravenous (iv) and intramuscular (im) administrations of 5 mg/kg bw to six healthy adult Angora rabbits. Plasma ENR concentrations were measured by high performance liquid chromatography. The pharmacokinetic data were best described by a two-compartment open model. ENR pharmacokinetic parameters were similar (p > 0.05) for iv and im administrations in terms of AUC(0-infinity)t(1/2 beta) and MRT. ENR was rapidly (t(1/2a), 0.05 h) and almost completely (F, 87%) absorbed after im injection. In conclusion, the pharmacokinetic properties of ENR following iv and im administration in Angora rabbits are similar to other rabbit breeds, and once or twice daily iv and im administrations of ENR at the dose of 5 mg/kg bw, depending upon the causative pathogen and/or severity of disorders, may be useful in treatment of infectious diseases caused by sensitive pathogens in Angora rabbits. (c) 2006 Elsevier Ltd. All rights reserved.
Pharmacokinetics of intravenous and intramuscular danofloxacin in red-eared slider turtles (Trachemys scripta elegans)
(JAPAN SOC VET SCI, 2019) Corum, Orhan; Corum, Duygu Durna; Altan, Feray; Er, Ayse; Cetin, Gul; Uney, Kamil
This study aimed to investigate the pharmacokinetics of danofloxacin in red-eared slider turtle (Trachemys scripta elegans) following a single intravenous (IV) and intramuscular (IM) administrations of 6 mg/kg, using a two-way crossover study with 30-day washout period. Eight clinically healthy red-eared slider turtle weighing 410-600 g (mean 490 g) were used for the study. Danofloxacin concentrations were measured using the reversed-phase high-performance liquid chromatography. The plasma concentration-time data were evaluated by a non-compartmental method. After IV administration, the elimination half-life (t(1/2 lambda z)), mean residence time (MRT0-8), area under the concentration-time curve (AUC(0-infinity)), volume of distribution at steady state and total body clearance in plasma were 24.17 hr, 30.64 hr, 143.31 hr center dot mu g/ml, 1.29 l/kg and 0.04 l/hr/kg, respectively. Following IM administration, t1/2.z, MRT0-infinity, AUC(0-infinity), peak concentration (C-max), time to reach Cmax, and bioavailability in plasma were 32.00 hr, 41.15 hr, 198.23 hr center dot mu g/ml, 8.75 mu g/ml, 1.5 hr and 139.89%, respectively. Danofloxacin has clinically superior pharmacokinetic properties, including the complete IM absorption, slow elimination and wide volume of distribution in redeared slider turtles. However, further pharmacokinetics/pharmacodynamics studies are necessary for the treatment of diseases caused by susceptible bacteria with known minimum inhibitory concentration values in red-eared slider turtles.

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