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Öğe 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, SemaÇalışma, 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.Öğe Amiodarone May Prevent the Tilmicosin-caused Lethal Toxicity(UNIV FED RIO GRANDE DO SUL, 2014) Er, Ayse; Tras, Bunyamin; Cetin, Gul; Dik, BurakBackground: Tilmicosin is widely used in veterinary medicine and its accidental overdose by injection may cause death via causing negative inotropy and positive chronotropy in both the treated animal and the veterinarian. In addition, there is no any antidote against to tilmicosin-caused death. Amiodarone blocks some channels in the heart, but it has much complex effect including vagotonic, bradycardic etc on the heart. Considering vagotonic and bradycardic effects of amiodarone, it has been hypothesised that amiodarone may prevent tilmicosin-caused death. The aim of this study was to determine the effect of amiodarone on the survival rate of rats in tilmicosin-caused lethal toxicity. Materials, Methods & Results: Twenty female Wistar rats (body weight: 288 +/- 33.8 g, age: 7-8 months) were used in this study. The study protocol was approved by the Ethical Committee. Rats received food and water ad libitum. The rats were divided into two groups containing 10 rats each. Rats in Group 1 were administered 360 mg/kg of tilmicosin in a single subcutaneous injection. Rats in Group 2 were administered 25 mg/kg of amiodarone via the tail vein at 8. min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg. After the injections, deaths were recorded at 0, 2, 6, 10, 12 and 24 h. At the end of the 24-h period, survival/death ratio was analysed by the Chi-square test. The level of statistical significance was set at P < 0.05. The survival rate of Group 2 (40%) was statistically significantly (P < 0.025) higher than that of Group 1 (0.0%). In control group all rats died at 10 h after subcutaneously tilmicosin injection. In Group 2 were administered 25 mg/kg of amiodarone (intravenously) at 8 min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg, and 2 rats died at 2 h and 4 rats died at 12 h. At the end of the experiment, all rats died in tilmicosin injected group whereas 4 rats lived in amiodarone and tilmicosin administered group. Clinically tilmicosin administered rats were observed as worse than amiodarone and tilmicosin administered group. Observed clinical signs of toxicity were fluffed feathers, ataxia, weakness in the legs, hypoactivity, lethargy. Discussion: Tilmicosin, a macrolide antibiotic, is widely used in the therapy of respiratory system infections in cattle and sheep. However, tilmicosin has cause serious cardiac side effects, and after tilmicosin administration to animals or accidental self-exposure of this drug to humans, if may cause heart related side effects including chest pain, increased serum cardiac damage markers, changed electrocardiogram, and decreased antioxidant enzyme activities in the heart, serum potassium level and death, as well as. Tilmicosin causes negative inotropy and positive chronotropy. Although the mechanism of tilmicosin-induced cardiotoxicity is not fully known, the inhibitory effect of tilmicosin on the entry of calcium into the cell may cause this lethal effect. It can be speculated that the beneficial effect of amiodarone in tilmicosin toxicity may primarily depend on the potassium channel blocking, antiarrhythmic effect and other exactly not explained effects. Amiodarone may increase survival rate and may be beneficial in the treatment of tilmicosin-caused lethal toxicity. However, especially specific cellular target or other effects of amiodarone on the heart are needed to determine in the tilmicosin toxicity.Öğe Comparative Pharmacokinetics and Metabolisms of Caffeine in Sheep Breeds(JAPAN SOC VET SCI, 2011) Uney, Kamil; Tras, BunyaminThe 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.Öğe The Disposition and Milk Levels of Sulfamethoxazole - Trimethoprim Combination After Intrauterine Administration in Lactating Cows During Post-Partum(Indian Veterinary Journal, 2000) Elmas, Muammer; Tras, Bunyamin; Bas, Ahmet levent; Yazar, Enver; Umitli, Seyit; Birdane, Yavuz OsmanThe sulphonamide-trimethoprim combinations are commonly used yia intrauterine administration in the therapy of genital diseases of large animals in Turkey (Elmas et a/., 1999; Kaya, 1998). Several workers have studied the absorption and elimination of various sulphonamidetrimethoprim combinations in different species (Chaudray et al., 1987; Boyd and Allen,,1989;Eimas etal., loc.cit }, However, no pharmacokinetic studies have been carried. out on the use of sulfamethoxazole (SMZ) - trimethoprim (TMP) in lactating cows during post-partum. We investigated the disposition of SMZ-TMP combination along with passing ratio to milk following intrauterine bolus administration in cows during, post-partum.Öğe 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, SemaThis 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.Öğe Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs(WILEY, 2019) Ozdemir, Zeynep; Faki, Hatice Eser; Uney, Kamil; Tras, BunyaminThe 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.Öğe 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, BunyaminThe 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.Öğe Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Angora rabbits(ELSEVIER SCI LTD, 2007) Elmas, Muammer; Uney, Kamil; Yazar, Enver; Karabacak, Ayse; Tras, BunyaminThe 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.Öğe Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite following intravenous administration in cattle(SPRINGER, 2019) Uney, Kamil; Tras, Bunyamin; Corum, Orhan; Yildiz, Ramazan; Maden, MehmetThis study investigated the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after single-dose intravenous (IV) administration (10mg/kg) of PTX in six healthy cattle. The safety of PTX was evaluated by clinical observation and biochemical analysis. Plasma concentrations of PTX and M-I were simultaneously determined by reverse-phase high performance liquid chromatography. Pharmacokinetic parameters were calculated using non-compartmental methods. Salivation and discomfort were observed for 2h following the drug administration. Serum direct bilirubin, total bilirubin, and phosphorus levels at 24h following the drug administration were significantly different from the control values (0h) (P<0.05). Pharmacokinetic variables of PTX were characterized by a short terminal elimination half-life (1.05 +/- 0.19h), a large volume of distribution (6.30 +/- 1.76L/kg), and high total body clearance (5.31 +/- 1.27L/h/kg). The mean ratio between the area under the concentration-time curves of M-I and PTX was 1.34. These results indicate that single-dose administration of PTX at 10mg/kg IV in cattle resulted in therapeutic concentrations similar to those observed in humans and horse. However, further studies are necessary to determine the safety and pharmacokinetics following repeated administrations of PTX.
