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Öğe 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, KamilThe 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.Öğe 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, KamilBackground 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.Öğe Effect of Age on the Pharmacokinetics of Marbofloxacin Following Intravenous Administration in Calves(Wiley, 2024) Corum, Orhan; Yuksel, Murat; Coskun, Devran; Corum, Duygu Durna; Kartal, Serafettin; Cellat, Mustafa; Uney, KamilThe aim of this study was to compare the pharmacokinetics of marbofloxacin after intravenous (IV) administration of a single dose of 10 mg/kg to calves of different ages. The study was carried on 1- (n = 6), 2- (n = 6), and 4-month-old (n = 6) Montofon calves. Plasma concentrations of marbofloxacin were measured using HPLC, and pharmacokinetic data were calculated by non-compartmental analysis. The elimination half-life (t(1/2 lambda z)), volume of distribution at steady state (V-dss), total clearance (Cl-T), and area under the concentration-versus time curve (AUC(0-infinity)) values of marbofloxacin in 1-month-old calves were 10.62 h, 1.03 L/kg, 0.08 L/h/kg, and 127.90 h*mu g/mL, respectively. While the t(1/2 lambda z) (from 10.62 to 3.36 h) and AUC(0-infinity) (from 127.90 to 47.35 h*mu g/mL) decreased in parallel with the age of the calves, Cl-T (from 0.08 to 0.21 L/h/kg) increased. The V-dss of marbofloxacin was higher in 1- and 2-month-old calves compared to 4-month-old calves. After IV administration of marbofloxacin at a dose of 10 mg/kg, an fAUC(0-24)/MIC90 ratio of >= 125 was obtained for bacteria with MIC90 values of <= 0.60, <= 0.39 and <= 0.27 mu g/mL in 1-, 2-, and 4-month-old calves, respectively. These results show that the antibacterial effect of marbofloxacin, which has concentration-dependent activity, decreases due to age-related pharmacokinetic changes and that the 10 mg/kg dose should be reviewed according to the MIC90 value of the bacteria.Öğe Effect of Body Size on Plasma and Tissue Pharmacokinetics of Danofloxacin in Rainbow Trout (Oncorhynchus mykiss)(Mdpi, 2024) Uney, Kamil; Corum, Duygu Durna; Marin, Pedro; Coskun, Devran; Terzi, Ertugrul; Badillo, Elena; Corum, OrhanDanofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 +/- 0.5 degrees C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t1/2 lambda z), volume of distribution (Vdarea/F), total clearance (CL/F), peak concentration (Cmax), and area under the plasma concentration-time curve (AUC0-last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 mu g/mL, and 82.46 h center dot mu g/mL, respectively. Plasma t1/2 lambda z, AUC0-last and Cmax increased concomitantly with trout growth, whereas CL/F and Vdarea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. Cmax and AUC0-last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 mu g/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue.Öğe Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep(Wiley, 2021) Cetin, Gul; Durna Corum, Duygu; Corum, Orhan; Atik, Orkun; Coskun, Devran; Uney, KamilIn this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 +/- 0.3 years and 44 +/- 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t(1/2 lambda z)), area under the plasma concentration-time curve from zero (0) hours to infinity (infinity) (AUC(0-infinity)), total clearance (Cl-T), and volume of distribution at steady state were 1.42 h, 182.41 h*mu g/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t(1/2 lambda z) and AUC(0-infinity) of ceftriaxone, they significantly reduced the Cl-T. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of <= 0.75 and <= 1 mu g/mL, respectively, in sheep with an inflammatory condition.Öğe Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)(Wiley, 2022) Corum, Orhan; Uney, Kamil; Corum, Duygu Durna; Atik, Orkun; Coskun, Devran; Zhunushova, Aidai; Elmas, MuammerThe aim of the study was to determine the effect of ketoprofen (2 mg/kg) on the intravenous pharmacokinetics of ganciclovir (10 mg/kg) in chukar partridges (Alectoris chukar). Eight clinically healthy partridges were used in the study. The study was performed in two periods using a cross-over design following a 15-day drug washout period. Plasma concentrations of ganciclovir were determined using the high-pressure liquid chromatography-ultraviolet detector and analyzed by non-compartmental analysis. The elimination half-life (t(1/2 lambda z)), area under the concentration-time curve (AUC(0-infinity)), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*mu g/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t(1/2 lambda z) and AUC(0-infinity) of ganciclovir by 78% and 108%, respectively, and while decreased Cl-T by 53%. The increased plasma concentration and prolonged elimination half-life of ganciclovir caused by ketoprofen may result in the prolonged duration of action and therapeutic effect of ganciclovir. However, the concomitant use requires determination of the pharmacokinetics of ketoprofen and the safety of both drugs.Öğe 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, OrhanCarprofen 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.Öğe Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration(Mdpi, 2023) Corum, Orhan; Uney, Kamil; Terzi, Ertugrul; Corum, Duygu Durna; Coskun, Devran; Altan, Feray; Elmas, MuammerSimple Summary Doxycycline, an approved aquacultural antibiotic, is extensively used in the treatment of bacterial diseases in fish. Since fish are poikilothermic organisms, their body temperature and metabolic rate are primarily influenced by the temperature of the water. Therefore, temperature may be affected by pharmacokinetic behavior and withdrawal times of drugs. The current study was undertaken to look at the differences in pharmacokinetics, tissue residues, and withdrawal times of doxycycline following oral administration in rainbow trout reared at 10 and 17 & DEG;C. The increment of water temperature from 10 to 17 & DEG;C decreased the elimination half-life, the body clearance, and the distribution volume of doxycycline and increased plasma concentrations. The withdrawal times for plasma and tissues decreased with the temperature increase. The results contributed to the determination of an optimal dosing regimen and the safe consumption of edible tissues in rainbow trout that were administered doxycycline and reared at different temperatures. The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 & DEG;C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 & DEG;C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration-time curve from 173.23 to 240.96 h * & mu;g/mL, and increased the peak plasma concentration from 3.48 to 5.50 & mu;g/mL. At 10 and 17 & DEG;C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 & mu;g/kg) and in Japan (50 & mu;g/kg), the withdrawal times of doxycycline at 10 and 17 & DEG;C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.Öğe Pharmacokinetics and bioavailability of carprofen in sheep(Wiley, 2022) Coskun, Devran; Corum, Orhan; Durna Corum, Duygu; Uney, Kamil; Elmas, MuammerThe aim of this study was to determine the pharmacokinetics and bioavailability of carprofen in sheep following single intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations of a parenteral formulation at a dose of 4 mg/kg. A total of eight sheep were used for the investigation. The study comprised four periods, according to a crossover design with a 21-day washout period between treatments. Plasma concentrations of carprofen were measured using HPLC-UV. Pharmacokinetic parameters were estimated by non-compartmental model analysis. Following IV administration, t(1/2 lambda z), Cl-T, and V-dss were 43.36 h, 1.98 ml/h/kg, and 121.36 ml/kg, respectively. The C-max(obs) was 26.57 mg/ml for the IM, 23.76 mg/ml for the SC, and 15.90 mg/ml for the PO. The bioavailability following IM, SC, and PO administrations was 75.47%, 82.00%, and 62.51%, respectively. Plasma creatine kinase activity increased significantly at 3, 6, and 12 h following IM administration of carprofen. Despite differences in plasma concentrations and bioavailability among administration routes, carprofen at 4 mg/kg dose may provide the plasma concentration (>1.5 mu g/ml) needed for analgesic effect during 144 h in all routes. However, because of the slow absorption rate after SC and PO routes, the IV route may be preferred primarily for the rapid onset in the analgesic and anti-inflammatory effect of carprofen in sheep. Despite the favorable kinetics, the muscle damage caused by IM injection limits use of carprofen via IM route.Öğe Pharmacokinetics and bioavailability of meloxicam in Pekin ducks following intravenous, intramuscular and oral administration(Elsevier, 2023) Coskun, Devran; Corum, Orhan; Corum, Duygu Durna; Uney, KamilObjective 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.Öğe Pharmacokinetics and Plasma Protein Binding of Flunixin in Rainbow Trout (Oncorhynchus mykiss)(Wiley, 2024) Uney, Kamil; Corum, Orhan; Corum, Duygu Durna; Coskun, Devran; Sakin, Fatih; Elmas, MuammerFlunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout (Oncorhynchus mykiss) maintained at 12 +/- 0.6 degrees C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High-pressure liquid chromatography-ultraviolet was employed to quantify flunixin concentrations. The elimination half-life (t(1/2 lambda z)) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t(1/2 lambda z) was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 +/- 0.41 mu g/mL at 4 h for oral administration and 13.98 +/- 0.86 mu g/mL at 2 h for IM administration. The in vitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 +/- 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.Öğe Pharmacokinetics of carprofen following single and repeated intravenous administrations of different doses in sheep(Wiley, 2022) Corum, Orhan; Coskun, Devran; Corum, Duygu Durna; Ider, Merve; Yildiz, Ramazan; Ok, Mahmut; Uney, KamilThe aim of this study was to determine the pharmacokinetics of carprofen following single and repeated intravenous (IV) administrations at 1.4 and 4 mg/kg doses in sheep. The study was carried out on twelve sheep in two experiments as single- and multiple-dose pharmacokinetics. In experiment 1, carprofen was administered via IV at single doses of 1.4 (n = 6) and 4 mg/kg (n = 6) in a randomized parallel design. In experiment 2, the same dose groups in experiment 1 following the 21-day washout period received intravenously carprofen every 24 h for 5 days. Plasma concentrations were measured using high-performance liquid chromatography-UV and analyzed by a two-compartment open model. After the single administration of 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 0.62 h, 27.57 h, 38.78 h, 2.72 ml/h/kg, 105.26 ml/kg, and 515.12 h*mu g/ml, respectively. Carprofen at a single dose of 4 mg/kg showed prolonged t(1/2el) and MRT, and increased V-dss. On day 5 after the repeated administration of the 1.4 mg/kg dose, the t(1/2 alpha), t(1/2el), MRT, Cl-T, V-dss, and AUC were 1.12 h, 57.48 h, 82.18 h, 0.55 ml/h/kg, 45.43 ml/kg, and 2532 h*mu g/ml, respectively. Carprofen at a repeated dose of 4 mg/kg showed increased Cl-T and V-dss and decreased AUC/dose. Although the long t(1/2 lambda z) in single and multiple IV dose studies suggest the possibility of its effective use, the IV route may not be practical in sheep. Therefore, oral and subcutaneous routes of carprofen in sheep would be more valuable in clinical settings.Öğe Pharmacokinetics of cefquinome in rainbow trout (Oncorhynchus mykiss) after intravascular, intraperitoneal, and oral administrations(Wiley, 2022) Corum, Duygu Durna; Corum, Orhan; Terzi, Ertugrul; Coskun, Devran; Bilen, Soner; Cetin, Gul; Uney, KamilThis study aimed to determine the pharmacokinetics and bioavailability of cefquinome in rainbow trout (Oncorhynchus mykiss) following intravascular (IV), intraperitoneal (IP), and oral (PO) administrations at 14 +/- 1 degrees C. In this study, three hundred and six clinically healthy rainbow trout (110-140 g) were used. The fish received single IV, IP, and PO injections of cefquinome at 10 mg/kg dose. The plasma concentrations of cefquinome were measured using HPLC-UV and were evaluated using non-compartmental analysis. Cefquinome was measured up to 96 h for PO route and 144 h for IV and IP routes in plasma. Following IV administration, t(1/2 lambda z), Cl-T, and V-dss were 18.85 h, 0.037 L/h/kg, and 0.84 L/kg, respectively. The C-max of IP and PO routes was 9.75 and 1.64 mu g/ml, respectively. The bioavailability following IP and PO administrations was 59.46% and 12.33%, respectively. Cefquinome at 10 mg/kg dose may maintain T > MIC above 40% at 72 and 96 h intervals, respectively, following the IP and IV routes for bacteria with MIC values of <= 2 mu g/ml and at 24 h intervals following the PO route for bacteria with MIC value of <= 0.75 mu g/ml. However, further studies are needed to determine in vitro and in vivo antibacterial efficacy and multiple dosage regimens of cefquinome against pathogens isolated from rainbow trout.Öğe Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep(Wiley, 2024) Corum, Orhan; Uney, Kamil; Coskun, Devran; Durna Corum, Duygu; Cetin, Gul; Elmas, MuammerObjective: This study aimed to investigate the plasma and milk pharmacokinetics, as well as the withdrawal time (WT) from milk of tolfenamic acid (2 and 4 mg/kg) following intravenous (IV) administration to eight healthy lactating Akkaraman sheep. Methods: The trial was conducted in two periods in accordance with a crossover pharmacokinetic design. The concentrations of tolfenamic acid in the plasma and milk were determined using high-pressure liquid chromatography and evaluated using non- compartmental analysis. The WT of tolfenamic acid in milk was calculated using the WT 1.4 software. Results: Compared to the 2 mg/kg dose, plasma volume of distribution at steady state (from 0.43 to 0.50 L/kg), terminal elimination half-life (from 2.41 to 4.14 h) and dose-normalized area under the plasma concentration-time curve (AUC(0-infinity), from 9.46 to 30.11 h mu g/mL) increased, whereas total body clearance (from 0.21 to 0.13 L/h/kg) decreased at the 4 mg/kg dose. The peak milk concentration (C-max) and AUC(0-infinity) values in milk were 0.26 mu g/mL and 0.28 h mu g/mL, respectively, for 2 mg/kg, and 0.43 mu g/mL and 0.55 h mu g/mL, respectively, for 4 mg/kg. Although the dose-normalized C-max of milk decreased depending on the dose, no difference was observed in dose-normalized AUC(0-infinity). The AUC(0-infinity milk)/AUC(0-infinity plasma) ratio was 0.03 for 2 mg/kg and 0.02 for 4 mg/kg. The WT values calculated for milk at dosages of 2 and 4 mg/kg were 3 and 4 h, respectively. Conclusions: A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians' decision-making processes.Öğe Potential antidiabetic activity of benzimidazole derivative albendazole and lansoprazole drugs in different doses in experimental type 2 diabetic rats(Tubitak Scientific & Technological Research Council Turkey, 2021) Dik, Burak; Coskun, Devran; Bahcivan, Emre; Uney, KamilAim: The aim of this study is to determine the effects of different concentrations of albendazole and lansoprazole, which were benzimidazole derivatives, on endocrinologic and biochemical parameters in experimental type 2 diabetic (T2D) rats. Materials and methods: In this study, 46 male Wistar Albino rats were used. Animals were divided as healthy control (0.1 mL/rat/day saline, s.c, n = 6), diabetes control (0.1 mL/rat/day saline, s.c, n = 8), diabetes+low-dose albendazole (5 mg/kg, oral, n = 8), diabetes+high-dose albendazole (10 mg/kg, oral n = 8), diabetes+low-dose lansoprazole (15 mg/kg, subcutaneous, n = 8), and diabetes+high-dose lansoprazole (30 mg/kg, subcutaneous, n = 8). All groups were treated for 8 weeks. The blood samples were analyzed by autoanalyzer and ELISA kits for biochemical and endocrinological parameters, respectively. Results: Glucose, HbA1c, triglyceride, low density cholesterol (LDL), leptin, and Homeostatic Model Assessment for insulin resistance (HOMA-IR) levels increased and insulin and HOMA-beta levels decreased in the diabetic rats compared to the healthy control group. The glucose, HbA1c, and triglyceride levels were partially decreased; however, insulin and HOMA-beta levels were increased by low-dose albendazole therapy. The high dose of lansoprazole treatment increased insulin level. Conclusion: The lansoprazole and albendazole treatments can be a potential drug or combined with antidiabetic drugs in T2D treatment by Adenosine 5'-monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor (PPAR), incretin-like effect and other antidiabetic mechanisms. It may be beneficial to create an effective treatment strategy by developing more specific substances with benzimidazole scaffold.
