Browsing by Author "Atik O."

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Effect of benzylpenicillin on intravenous pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans)
(2020-07-01) D. Corum D.; Corum O.; Atik O.; E. Faki H.; Altan F.; Uney K.
The aim of this study was to determine the effect of benzylpenicillin on the pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans). Six clinically healthy red-eared slider turtles weighing 400 and 580 g were used for the study. Acyclovir (40 mg/kg) and benzylpenicillin (30 mg/kg) were administered intravenously to turtles. In the study, the cross-pharmacokinetic design (2 × 2) with a 30-day washout period was performed in two periods. Plasma concentrations of acyclovir were assayed using the high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by two-compartment open pharmacokinetic model. Following the administration of acyclovir alone, elimination half-life (t1/2β), area under the plasma concentration–time curve (AUC), total clearance (ClT), and volume of distribution at steady-state (Vdss) were 20.12 hr, 1,372 hr * µg/mL, 0.03 L hr−1 kg−1, and 0.84 L/kg, respectively. Benzylpenicillin administration increased t1/2β, AUC, and Vdss while decreased ClT of acyclovir. These results showed that benzylpenicillin changed the pharmacokinetics of acyclovir following simultaneous administration in turtles. However, further research is needed to determine molecular mechanism of interaction in turtle.
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.
Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)
(2022-01-01) Corum O.; Uney K.; Durna Corum D.; Atik O.; Coskun D.; Zhunushova A.; Elmas M.
The 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 (t1/2ʎz), area under the concentration-time curve (AUC0-∞), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*μg/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t1/2ʎz and AUC0-∞ of ganciclovir by 78% and 108%, respectively, and while decreased ClT 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.
Pharmacokinetics and bioavailability of ceftriaxone in brown trout (Salmo trutta fario) after intravenous and intramuscular administration
(2019-02-01) Corum O.; Er A.; Durna Corum D.; Atik O.; Uney K.
Ceftriaxone (CTX) is a third-generation cephalosporin that has proven to be effective in the treatment of infections caused by a wide range of gram-positive and gram-negative microorganisms. This study aimed to determine the plasma and muscle pharmacokinetics of CTX after its administration via the intravenous (IV) and intramuscular (IM) routes to brown trout (Salmo trutta fario) at temperatures of 10 °C–13 °C. In total, 140 healthy brown trout (body weight, 245 ± 38 g) were used. The brown trout received single IV and IM injections of CTX at 25 mg/kg. The IV doses were injected into the caudal vein, whereas the IM doses were injected into the right epaxial muscles. The plasma and muscle tissue concentrations of CTX were measured using high-performance liquid chromatography. Pharmacokinetic parameters were calculated using noncompartmental methods. Following the IV administration of CTX, the elimination half-life (t1/2ʎz), volume of distribution at steady state, total body clearance, and area under the concentration–time curve (AUC0–72) in plasma were 5.83 h, 0.09 L/kg, 0.02 L/h/kg, and 1079.46 h*μg/mL, respectively. After the IM administration of CTX, plasma t1/2ʎz, peak plasma concentration (Cmax), time to reach Cmax, and bioavailability were 22.78 h, 87.92 μg/mL, 0.5 h, and 27.19%, respectively. The AUCMuscle/AUCPlasma ratio following the IV administration was 0.02 and that following the IM administration was 0.04. CTX exhibited low bioavailability and prolonged t1/2ʎz after the IM administration. The prolonged t1/2ʎz of CTX could thus be beneficial in brown trout. Nevertheless, future studies that aim to determine the clinical efficacy and pharmacokinetics after repeated administration of CTX are warranted.
Pharmacokinetics and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous, intramuscular, subcutaneous, and oral administrations
(2019-03-01) Corum O.; Durna Corum D.; Atik O.; Eser Faki H.; Altan F.; Uney K.
The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15-day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed-phase high-performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half-life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady-state following IV administration were 0.13 L hr −1 kg −1 and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.
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 and bioavailability of marbofloxacin in lambs following administration of intravenous, intramuscular and subcutaneous
(2018-02-01) Altan F.; Corum O.; Corum D.D.; Atik O.; Uney K.
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 (t1/2ʎz) 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 μg/mL), in lambs since high AUC0-24/MIC and Cmax/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 danofloxacin in rainbow trout after different routes of administration
(2020-04-15) Terzi E.; Corum O.; Bilen S.; Kenanoglu O.N.; Atik O.; Uney K.
The pharmacokinetics of danofloxacin was studied in rainbow trout (Oncorhynchus mykiss) after single administration by intravenous (IV), intramuscular (IM) and oral (OR) gavage at a dose of 10 mg/kg and by 10 mg/L bath for 2 h at 11.7 ± 0.8 °C. Furthermore, minimal inhibitory concentrations (MICs) of danofloxacin against a pathogenic strain of Yersinia ruckeri, Pseudomonas spp., and Aeromonas hydrophila were determined. Plasma concentrations of danofloxacin were determined using high-performance liquid chromatograph - UV and further subjected to noncompartmental analysis. Elimination half-lives for IV, IM, OR and bath administration were 25.97 h, 42.43 h, 41.04 h and 40.41 h, respectively. Peak plasma concentrations (Cmax) for IM, OR and bath administration were 3.64 ± 0.12, 2.93 ± 0.23, and 0.36 ± 0.02 μg/mL, respectively. Bioavailability was 105.87% (IM), 96.92% (OR) and 10.09% (bath). MIC values were 0.02 μg/mL for Y. ruckeri, 3.2 μg/mL for Pseudomonas spp., and 8 μg/mL for A. hydrophila at 12 °C. Danofloxacin provides the desired AUC0–24/MIC (≥125) and Cmax/MIC (≥10) values for Y. ruckeri following administration at a dose of 10 mg/kg (L) from all routes administration, whereas inadequate for Pseudomonas spp. and A. hydrophila. This information may help in the use of danofloxacin in rainbow trout, but increasing doses pharmacokinetics with the residue depletion study and clinical studies in infected fish are needed.
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 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 levamisole in the red-eared slider turtles (Trachemys scripta elegans)
(2019-11-01) Corum O.; Durna Corum D.; Atik O.; Altan F.; Er A.; Uney K.
The pharmacokinetics and bioavailability of levamisole were determined in red-eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three-way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high-performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half-life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr−1 kg−1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of Tmax. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t1/2ʎz, can be recommended as an effective way for treating nematodes in turtles.
Pharmacokinetics of pentoxifylline and its 5-hydroxyhexyl metabolite after intravenous administration of increasing doses to sheep
(2019-07-01) Corum O.; Corum D.D.; Atik O.; Er A.; Uney K.
OBJECTIVE To determine the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl metabolite (M-I) after IV administration of increasing doses of PTX to sheep. ANIMALS 6 healthy adult Merino sheep. PROCEDURES Each sheep received 10-, 20-, and 40-mg/kg doses of PTX, IV, with a 15-day washout period between doses. Blood samples were collected before and at predetermined times after administration of each dose to determine plasma PTX and M-I concentrations by high-performance liquid chromatography. Pharmacokinetic parameters for PTX and M-I were estimated by noncompartmental analysis. RESULTS No adverse effects were observed after administration of the 10- and 20-mg/kg doses. Following administration of the 40-mg/kg dose, all sheep developed tachycardia and hypersalivation and appeared agitated for approximately 4 hours. Plasma PTX concentrations considered therapeutic in other species were achieved in all sheep after administration of all 3 doses. Pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner. For PTX, the mean area under the concentration-time curve (AUC), elimination half-life, and volume of distribution increased with dose and ranged from 15.67 to 94.66 h.µg/mL, 0.68 to 0.91 hours, and 0.55 to 0.66 L/kg, respectively, whereas clearance decreased with dose and ranged from 0.42 to 0.64 L/h/kg. The mean ratio of the AUC for M-I to AUC for PTX ranged from 0.38 to 0.46. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that pharmacokinetic parameters for PTX and M-I varied in a dose-dependent linear manner in healthy sheep. Further studies are warranted to determine the therapeutic threshold and optimal dosage for PTX in sheep. (Am J Vet Res 2019;80:702-708).
Pharmacokinetics of tolfenamic acid in red-eared slider turtles (Trachemys scripta elegans)
(2019-09-01) Corum O.; Atik O.; Durna Corum D.; Er A.; Uney K.
Objective: To determine the pharmacokinetics of tolfenamic acid (TA) after different routes of administration [intravenous (IV) and intramuscular (IM), 2 mg kg−1] and doses (IV, 2 and 4 mg kg−1) in red-eared slider turtles (Trachemys scripta elegans). Study design: Randomized experimental trial. Animals: Sixteen healthy red-eared slider turtles. Methods: Turtles were randomly assigned to two groups (n = 8 each). Group 1 received TA at a dose of 2 mg kg−1 IV and then IM, after a washout period of 30 days. Group 2 received 4 mg kg−1 TA IV. A noncompartmental analysis was used to calculate pharmacokinetic variables. Results: No local and/or systemic adverse drug effects were observed in any turtle. Elimination half-life and mean residence time following IM administration at 2 mg kg−1 were significantly longer than those following IV administration. The bioavailability following IM administration was complete. The area under the plasma concentration-time curve, elimination half-life, mean residence time and total clearance were significantly different between the dose groups. Conclusions and clinical relevance: The absence of adverse reactions in the turtles of the study of TA along with the favourable pharmacokinetic properties (the long half-life and the complete bioavailability) of TA administered at the single doses of 2 and 4 mg kg−1 suggest the possibility of its effective use in turtles. However, further studies are required to establish a multiple dosage regimen of TA and to evaluate the clinical efficacy of administering TA.
The pharmacokinetics of letrozole and its effect on gonadotropins in anestrous ewes
(2021-12-01) Kivrak M.B.; Corum O.; Alkan H.; Atik O.; Aydin I.; Uney K.
The aim of this study was to determine the pharmacokinetics of letrozole and its effect on FSH and LH concentrations after single (IV, IM, SC) and repeated IV doses in anestrous ewes. This study was conducted in experiments 1 and 2 by randomly dividing 24 healthy Akkaraman ewes in anestrus into two equal groups. In experiment 1, the pharmacokinetics of letrozole following single IV, IM, and SC administration at 1 mg/kg dose and its effect of a single IV dose on plasma FSH and LH concentration were determined. In experiment 2, the effect of repeated IV doses of letrozole on FSH and LH concentrations was established. Plasma concentration of letrozole was measured using high-performance liquid chromatography, and pharmacokinetic parameters were calculated by non-compartmental analysis. FSH and LH concentrations were quantified using ELISA. The elimination half-life (t1/2ʎz) for IV, IM, and SC routes were 9.94, 37.29, and 41.07 h, respectively. The IV route for letrozole had a total clearance of 0.11 L/h/kg and a volume of distribution at a steady state of 1.50 L/kg. The peak plasma concentration was 0.11 μg/mL for the IM route and 0.14 μg/mL for the SC routes. The bioavailability was 55.18% for the IM route and 75.34% for the SC route. Letrozole following single and repeated (every 24 h for 3 days) IV administrations at 1 mg/kg dose did not affect LH concentration in anestrous ewes but caused an increase in the FSH concentration. This increase in FSH concentration may create a potential for the use of letrozole in ovarian superstimulation protocols. Favorable pharmacokinetic properties (long t1/2ʎz and good bioavailability) of letrozole for IM and SC routes require further investigation before use in estrus induction or estrus synchronization protocols in sheep.