Browsing by Author "Cetin G."

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A cardioprotective role of Nerium oleander with the expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue
(2018-01-01) Hitit M.; Corum O.; Corum D.D.; Donmez H.; Cetin G.; Dik B.; Er A.
Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes. Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P > 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P < 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P < 0.05) although it was lower in group 3 and 4 than in group 2 (P < 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P > 0.05). Copper (Cu) SOD mRNA was equally expressed in both the control group and group 2 (P > 0.05) but was lower in group 3 and 4 than in group 2 (P < 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression of HIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P > 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P > 0.05); however, it was higher in group 3 than in the control (P < 0.05) and tended to be higher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P > 0.05). Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.
Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep
(2021-11-01) Cetin G.; Durna Corum D.; Corum O.; Atik O.; Coskun D.; Uney K.
In 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 (t1/2ʎz), area under the plasma concentration–time curve from zero (0) hours to infinity (∞) (AUC0-∞), total clearance (ClT), and volume of distribution at steady state were 1.42 h, 182.41 h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t1/2ʎz and AUC0-∞ of ceftriaxone, they significantly reduced the ClT. 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 μg/mL, respectively, in sheep with an inflammatory condition.
Inﬂuences of tolfenamic acid and ﬂunixin meglumine on the disposition kinetics of levoﬂoxacin in sheep
(2020-03-01) Corum D.D.; Corum O.; Yildiz R.; Faki H.E.; Ider M.; Cetin G.; Uney K.
The pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration-time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h 3 mg/mL, respectively. Tolfenamic acid and ﬂunixin meglumine caused a slow elimination and increased plasma concentrations of levoﬂoxacin in combination administration. Levoﬂoxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and ﬂunixin meglumine for the therapy of infections and inﬂammatory conditions in sheep.
Pharmacokinetics and bioavailability of furosemide in sheep
(2021-07-01) Durna Corum D.; Corum O.; Atik O.; Cetin G.; Zhunushova A.; Uney K.
The pharmacokinetics and bioavailability of furosemide were determined following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at 2.5 mg/kg dose in sheep. The study was conducted on six healthy sheep in a three-way, three-period, crossover pharmacokinetic design with a 15-day washout period. In first period, furosemide was randomly administered via IV to 2 sheep, IM to 2 sheep and SC to 2 sheep. In second and third periods, each sheep received furosemide via different routes of administration with the 15-day washout period. Plasma concentrations were determined using a high-performance liquid chromatography assay and analyzed by noncompartmental method. The mean total clearance and volume of distribution at steady state following IV administration were 0.24 L h-1 kg-1 and 0.17 L/kg, respectively. The elimination half-life was similar for all administration routes. The mean peak plasma concentrations of IM and SC administration were 10.33 and 3.18 μg/ml at 0.33 and 0.42 hr, respectively. The mean bioavailability of IM and SC administration was 97.91% and 37.98%, respectively. The IM injection of furosemide may be the alternative routes in addition to IV. However, further research is required to determine the effect of dose and route of administration on the clinical efficacy of furosemide in sheep.
Pharmacokinetics of cefquinome in rainbow trout (Oncorhynchus mykiss) after intravascular, intraperitoneal, and oral administrations
(2022-11-01) Durna Corum D.; Corum O.; Terzi E.; Coskun D.; Bilen S.; Cetin G.; Uney K.
This 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°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, t1/2ʎz, ClT, and Vdss were 18.85 h, 0.037 L/h/kg, and 0.84 L/kg, respectively. The Cmax of IP and PO routes was 9.75 and 1.64 μg/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 μg/ml and at 24 h intervals following the PO route for bacteria with MIC value of ≤0.75 μg/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.
Pharmacokinetics of furosemide in goats following intravenous, intramuscular, and subcutaneous administrations
(2021-11-01) Cetin G.; Corum O.; Durna Corum D.; Atik O.; Turk E.; Tekeli I.O.; Uney K.
Furosemide, a loop diuretic drug, is recommended for use in cases of edema, ascites, congestive heart failure, toxicosis, and acute renal failure in goats. However, its pharmacokinetics and bioavailability have not been reported yet in this species. The aim of this study was to determine the pharmacokinetics and bioavailability of furosemide in goats following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations at a dose of 2.5 mg/kg. Six clinically healthy goats received furosemide by each route in a three-way crossover pharmacokinetic design with a 15-day washout period between administrations. The plasma concentrations of furosemide were determined using the high-performance liquid chromatography-UV method and analyzed by non-compartmental analysis. The elimination half-life following IV, IM, and SC administration was 0.71 (0.67–0.76) h, 0.69 (0.61–0.74) h, and 0.70 (0.67–0.79) h, respectively. The volume of distribution at steady state and total clearance for the IV route were 0.17 (0.16–0.19) L/kg and 0.30 (0.27–0.33) L/h/kg, respectively. The peak plasma concentrations of furosemide following IM and SC administrations were 11.19 (10.33–11.95) and 6.49 (5.92–7.00) μg/ml at 0.23 (0.16–0.25) and 0.39 (0.33–0.42) h, respectively. The bioavailability was 109.84 (104.92–116.99)% and 70.80 (55.77–86.67)% for the IM and SC routes, respectively. The pharmacokinetics of furosemide following the IV, IM, and SC administrations in goats demonstrated significant differences, which may have clinical and toxicological implications requiring further investigations.
Pharmacokinetics of intravenous and intramuscular danofloxacin in red-eared slider turtles (Trachemys scripta elegans)
(2019-05-01) Corum O.; Corum D.D.; Altan F.; Er A.; Cetin G.; Uney K.
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 (t1/2ʎz), mean residence time (MRT0-∞), area under the concentration-time curve (AUC0-∞), volume of distribution at steady state and total body clearance in plasma were 24.17 hr, 30.64 hr, 143.31 hr·μg/ml, 1.29 l/kg and 0.04 l/hr/kg, respectively. Following IM administration, t1/2ʎz, MRT0-∞AUC0-∞,peak concentration (Cmax), time to reach Cmax, and bioavailability in plasma were 32.00 hr, 41.15 hr, 198.23 hr·μg/ml, 8.75 μg/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.
Pharmacokinetics of intravenous meloxicam, ketoprofen and tolfenamic acid in chukar partridge (Alectoris chukar)
(2022-01-01) Cetin G.; Corum O.; Corum D.D.; Atik O.; Altan F.; Turk E.; Tekeli I.O.; Faki H.E.; Uney K.
1. The aim of this study was to determine the pharmacokinetics of meloxicam (MLX, 1 mg/kg body weight (BW)), ketoprofen (KETO, 2 mg/kg BW), and tolfenamic acid (TA, 2 mg/kg BW) in chukar partridge (Alectoris chukar) following intravenous (IV) administration. 2. Twenty-four healthy chukar partridges were randomly divided into three equal groups (n = 8) as MLX, KETO and TA. Plasma concentrations of MLX, KETO and TA were measured using high-performance liquid chromatography−ultraviolet detection and analysed using non-compartmental analysis. 3. No adverse effects were determined in chukar partridges after IV administration of MLX, KETO and TA. MLX, KETO and TA were detected in plasma up to 10, 12 and 12 h, respectively. The terminal elimination half-life of MLX, KETO and TA was 1.22, 1.77 and 1.95 h, respectively. MLX, KETO and TA exhibited volumes of distribution at a steady-state of 0.03, 0.23 and 0.41 l/kg BW, respectively. The total plasma clearance of MLX, KETO and TA was 0.02, 0.11 and 0.15 l/h/kg, respectively. The extraction ratios for MLX, KETO and TA were calculated as 0.002, 0.011 and 0.016, respectively. 4. MLX, KETO and TA offer treatment in chukar partridges for various conditions with an absence of adverse reactions and properties such as short elimination half-life and low volume of distribution. However, there is a need to establish the safety and adverse effects of repeated administration, pharmacokinetics of other administration routes and pharmacological efficacy of MLX, KETO and TA in chukar partridges.
Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica)
(2021-05-01) Turk E.; Tekeli I.O.; Corum O.; Durna Corum D.; Kirgiz F.C.; Cetin G.; Arslan Atessahin D.; Uney K.
The aim of this study was to determine the pharmacokinetics of meloxicam (MLX), carprofen (CRP), and tolfenamic acid (TA) in Japanese quails (Coturnix coturnix japonica) following intramuscular (IM) and oral administration at doses of 1, 10, and 2 mg/kg, respectively. A total of 72 quails were randomly divided into 3 equal groups as MLX, CRP, and TA. Each group was separated into two sub-groups that received IM and oral administration of each drug. Plasma concentrations of MLX, CRP, and TA were determined using HPLC-UV and analyzed by non-compartmental method. The t1/2ʎz and MRT of MLX, CRP, and TA after oral administration were similar to those after IM administration. The Vdarea/F of MLX, CRP, and TA after IM administration was 0.28, 2.05, and 0.20 L/kg. The Cl/F of MLX, CRP, and TA after IM administration was 0.12, 0.19, and 0.09 L/h/kg. MLX, CRP, and TA after oral administration showed significantly lower Cmax and longer Tmax compared with IM administration. The relative bioavailability of MLX, CRP, and TA following oral administration in quails was 76.13%, 61.46%, and 57.32%, respectively. The IM and oral route of MLX, CRP, and TA can be used for the treatment of various conditions in quails. However, further research is necessary to determine the pharmacodynamics and safety of MLX, CRP, and TA before use in quails.