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    Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep
    (Wiley, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Cetin, Gul; Irmak, Mehmet; Ceyhan, Hatice Rumeysa; Uney, Kamil
    The pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month- old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 +/- 0.91 kg), 6 months old (27.47 +/- 4.91 kg), and 12 months old (37.10 +/- 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (Vdss) and total body clearance (ClT) were significantly higher in 1- month- old (304.87 mL/kg and 16.57 mL/h/kg) than in 12- month- old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration- time curve from 0 to 72 h value of meloxicam was lower in 1- month- old (58.51 h*mu g/mL) compared to 12- month- old (92.59 h*mu g/mL) sheep. There was no difference in t1/ 2.z value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in Vdss and ClT in 12- month- old compared to 1- month- old sheep. Compared to 1- month- old and 12- month- old sheep, there was no difference in these parameters in 6- month- old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.
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    Comparative Pharmacokinetics of Intravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep
    (Bentham Science Publ Ltd, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Uney, Kamil
    Background Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target-age animals. Objective To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC-UV and analyzed using a non-compartmental method. Results ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t(1/2 lambda z) and V-dss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC(0-infinity CIP)/AUC(0-infinity ENR) ratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion The most important pharmacokinetic changes associated with aging in sheep are decreased V-dss and t(1/2 lambda z) of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC(0-24)/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 mu g/mL and for S. aureus (>30) with MIC of 0.5 mu g/mL in all ages of sheep.
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    Effect of Xylazine on Pharmacokinetics and Physiological Efficacy of Intravenous Carprofen in Castrated Goats Kids
    (Mdpi, 2023) Uney, Kamil; Yuksel, Murat; Corum, Duygu Durna; Coskun, Devran; Turk, Erdinc; Dingil, Hasan Basri; Corum, Orhan
    Carprofen can be used in the castration process of male goats due to its low side effects, long elimination half-life, and long-term effect. However, no studies were found on the pharmacokinetics and physiological efficacy of carprofen when employed for castration in male goats. The aim of this study was to determine the effect of xylazine (0.05 mg/kg, intramuscular) on the pharmacokinetics and physiological efficacy following intravenous administration of carprofen (4 mg/kg, intravenous) in male goat kids castrated using the burdizzo method. Thirty male Kilis goat kids (5-6 months and 18-30 kg of body weight) were randomly assigned to five groups (n = 6) as follows: healthy control (HC), castration control (CAST), castration+carprofen (CAST+CRP), castration+xylazine (CAST+XYL), and castration+xylazine+carprofen (CAST+XYL+CRP). Plasma concentrations of carprofen were analyzed via a non-compartmental method. Physiological parameters including serum cortisol, scrotal temperature, rectal temperature, and scrotal circumference were determined. Xylazine caused a decrease in the volume of distribution and clearance and an increase in the area under the curve of carprofen in CAST+XYL+CRP group (p < 0.05). The mean cortisol concentrations in CAST+CRP and CAST+XYL remained lower compared to CAST (p < 0.05). The mean cortisol concentrations in CAST+XYL+CRP were lower than in CAST+CRP and CAST+XYL (p < 0.05). In addition, the effect of carprofen administration alone on reducing the initial cortisol response to castration was observed from 6 to 48 h, while in combination with xylazine, it was observed immediately up to 48 h. No treatment differences were observed in rectal temperature, scrotal temperature, and scrotal circumference (p > 0.05). Xylazine caused an increase in plasma concentration and a decrease in clearance of carprofen after co-administration. However, when the effect of the combined administration of carprofen with xylazine on cortisol is evaluated, their combined use in castration process may be beneficial.
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    Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration
    (Elsevier, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Uney, Kamil
    Objective To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg(-1) in Pekin ducks.Study design Randomized experimental trial.Animals A total of 18 clinically healthy male Pekin ducks.Methods Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg(-1)) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.Results No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg(-1) and 6.68 mL kg(-1) hour(-1), respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (C-max), time to reach C-max and bioavailability (p < 0.05).Conclusions and clinical relevance Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.
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    Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep
    (Wiley, 2024) Gungor, Huseyin; Corum, Orhan; Corum, Duygu Durna; Kumru, Alper Serhat; Yilmaz, Gokhan; Coskun, Devran; Coskun, Alparslan
    The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that V(dss )decreased and C-0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 mu g/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of >= 1 mg/kg in sheep.