Browsing by Author "Durna Corum D."

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Effect of castration procedure on the pharmacokinetics of meloxicam in goat kids
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Uney K.
The aim of this study was to determine the changes in the pharmacokinetics of meloxicam in goat kids who were castrated following the administration of xylazine. Six goat kids were used for the study. The study was performed in two periods according to a longitudinal study, with a 15-day washout period between periods. In the first period (Control group), 1 mg/kg meloxicam was administered by i.v. route to kids. In the second period (Castration group), the kids were sedated with 0.3 mg/kg xylazine and castration was performed following meloxicam administration. Plasma meloxicam concentration was analyzed using HPLC-UV, and pharmacokinetic parameters were calculated by noncompartmental model. In the control group following the administration of meloxicam, mean elimination half-life (t1/2ʎz), area under the concentration–time curve (AUC0−∞), total body clearance (ClT), and volume of distribution at steady-state (Vdss) were 13.50 ± 0.62 hr, 41.10 ± 2.86 hr µg/ml, 24.43 ± 1.75 ml hr−1 kg−1, and 0.45 ± 0.03 L/kg, respectively. In the castration group, the t1/2ʎz of meloxicam prolonged, AUC0−∞ increased, and ClT and Vdss decreased. In conclusion, the excretion of meloxicam from the body slowed and the t1/2ʎz was prolonged in the castrated goat kids following xylazine administration. However, there is a need to determine the pharmacodynamics of meloxicam in castrated goat kids.
Effect of dose on the intravenous pharmacokinetics of tolfenamic acid in goats
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Kirgiz F.C.; Uney K.
The objective of this study was to determine the pharmacokinetics of tolfenamic acid (TA) following intravenous (IV) administration at doses of 2 and 4 mg/kg in goats. In this study, six healthy goats were used. TA was administered intravenously to each goat at 2 and 4 mg/kg doses in a cross-over pharmacokinetic design with a 15-day washout period. Plasma concentrations of TA were analyzed using the high performance liquid chromatography with ultraviolet detector, and pharmacokinetic parameters were assigned by noncompartmental analysis. Following IV administration at dose of 2 mg/kg, area under the concentration–time curve (AUC0−∞), elimination half-life (t1/2ʎz), total clearance (ClT) and volume of distribution at steady state (Vdss) were 6.64 ± 0.81 hr*µg/ml, 1.57 ± 0.14 hr, 0.30 ± 0.04 L h-1 kg-1 and 0.40 ± 0.05 L/kg, respectively. After the administration of TA at a dose of 4 mg/kg showed prolonged t1/2ʎz, increased dose-normalized AUC0-∞, and decreased ClT. In goats, TA at 4 mg/kg dose can be administered wider dose intervals compared to the 2 mg/kg dose. However, further studies are needed to determine the effect of different doses on the clinical efficacy of TA in goats.
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 co-administration on pharmacokinetics of cefquinome following repeated administration in goats
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Kirgiz F.C.; Sakin F.; Uney K.
The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t1/2ʎz), area under the concentration–time curve (AUC0–24), peak concentration (Cmax), apparent volume of distribution (Vdarea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0–24 and Cmax, and decreased Vdarea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats 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.
Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration
(2023-06-01) Corum O.; Uney K.; Terzi E.; Durna Corum D.; Coskun D.; Altan F.; Elmas M.
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 °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 °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 * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °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 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °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.
Gender Differences in the Effect of Calcitriol on the Body Disposition and Excretion of Doxorubicin in Mice
(2020-10-01) Durna Corum D.; Uney K.
Background and Objective: The antitumor activity and toxicity of doxorubicin are potentiated and attenuated by calcitriol, respectively. Potentially, calcitriol can be combined with doxorubicin for clinical benefit in chemotherapy. To gain insight into the interaction between doxorubicin and calcitriol, proposed for combined use in cancer treatment, we studied calcitriol's effect on the plasma pharmacokinetics, tissue distribution and excretion of doxorubicin in female and male mice. Methods: The control and calcitriol-treated groups, including an equal number of both sexes, received corn oil and calcitriol (2.5 μg/kg), respectively, intraperitoneally every other day for 8 days. At day 9, doxorubicin was administered intraperitoneally at a 6 mg/kg dose to each group. Doxorubicin concentrations in biologic specimens were determined by a high-performance liquid chromatographic-ultraviolet detector and analyzed using a non-compartmental model. Results: The plasma pharmacokinetics of doxorubicin were similar in the control and calcitriol-treated groups. While calcitriol did not alter the area under the plasma concentration-time curves (AUCs) and peak concentrations (Cmax) of doxorubicin in the small intestine and testis, it significantly reduced the AUCs and Cmax of doxorubicin in the lung, kidney, spleen, liver, stomach and ovaries. However, calcitriol increased the AUCs and Cmax of doxorubicin in the heart of females, brain of males and duodenum content and vitreous humor of female and male mice. The percent cumulative urine and fecal amounts of doxorubicin in calcitriol-treated mice were higher at 89.23% and 29.37% for female mice and 118.57% and 41.65% for male mice than those in the control mice, respectively. Conclusions: The tissue concentrations and excretion of doxorubicin in both female and male mice are influenced by calcitriol without changes in the plasma pharmacokinetics. The results from this study can provide insights to help obtain the optimal drug combination effects of doxorubicin with calcitriol in cancer treatment.
Pharmacokinetic/pharmacodynamic integration of marbofloxacin after oral and intravenous administration in rainbow trout (Oncorhynchus mykiss)
(2020-01-01) Corum O.; Terzi E.; Durna Corum D.; Kenanoglu O.; Bilen S.; Uney K.
The pharmaco-kinetic/dynamic of marbofloxacin was investigated after single intravenous (IV) and oral administration of 10 mg/kg in 192 healthy rainbow trout at 13 ± 1.2 °C. The plasma concentrations of marbofloxacin were determined by high-performance liquid chromatography-ultraviolet detection. After IV and oral administration, the plasma concentration–time data were described by a noncompartmental analysis. The minimal inhibitory concentration (MIC) of marbofloxacin against Yersinia ruckeri, Aeromonas hydrophila, Pseudomonas fluorescens and P. putida were determined by broth dilution method at 13 °C. After IV administration, the elimination half-life (t1/2ʎz), area under the concentration-versus time curve (AUC0-∞), apparent volume of distribution at steady-state and total body clearance of marbofloxacin were 18.05 h, 354.63 h ∗ μg/mL, 0.65 L/kg and 0.03 L/h/kg, respectively. After oral administration, t1/2ʎz, AUC0-∞, the peak plasma concentration, time of maximum concentration and bioavailability were 27.51 h, 135.29 h ∗ μg/mL, 3.74 μg/mL, 4 h and 38.15%, respectively. The respective MICs of marbofloxacin against Y. ruckeri, A. hydrophila, P. fluorescens and P. putida were determined as 0.02 μg/mL, 2.5 μg/mL, 2.5 μg/mL and 5 μg/mL, respectively. Following IV and oral administration of 10 mg/kg marbofloxacin, AUC/MIC and Cmax/MIC values were above the target levels for Y. ruckeri, while this dose was not sufficient for A. hydrophila and Pseudomonas spp. Because the pharmacokinetics and pharmacodynamics of a drug in fish are significantly affected by temperature, the dosage regimen of marbofloxacin should be modified according to temperature.
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 meloxicam in rainbow trout (Oncorhynchus mykiss) broodstock following intravascular, intramuscular, and oral administrations
(2022-03-01) Corum O.; Terzi E.; Durna Corum D.; Uney K.
The pharmacokinetics and bioavailability of meloxicam were investigated after single intravascular (IV), intramuscular (IM), and oral dose of 1 mg/kg in rainbow trout broodstock at 11 ± 1.2°C. A total of 36 healthy rainbow trout (Oncorhynchus mykiss) broodstock weighing 1.40 ± 0.26 kg was used for the investigation. Plasma concentrations of meloxicam were measured with high-performance liquid chromatography-ultraviolet detection, and pharmacokinetic parameters were calculated by non-compartmental analysis. The elimination half-life for IV, IM, and oral routes was 3.63, 4.55, and 2.95 h, respectively. The IV route for meloxicam showed the total clearance of 0.05 L/h/kg and volume of distribution at a steady state of 0.20 L/kg. The peak plasma concentration was 2.97 μg/ml for the IM route and 0.84 μg/ml for the oral route. The bioavailability was 78.45% for the IM route and 21.48% for the oral route. Meloxicam following IM and oral administration displayed short t1/2ʎz. The short t1/2ʎz could be an advantage for the short-term use in acute conditions. The IM route with the good bioavailability can be preferred for the treatment of various conditions. However, developing new oral formulations with the good bioavailability for meloxicam is necessary to minimize stress and trauma through minimal handling in rainbow trout broodstock.
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 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 marbofloxacin following intramuscular administration at different doses in sheep
(2019-05-01) Altan F.; Corum O.; Durna Corum D.; Altan S.; Uney K.
The pharmacokinetics of marbofloxacin (MBX) was determined following the intramuscular administration at the doses of 2, 4, 6, and 10 mg/kg in twenty-four healthy sheep. In parallel design, sheep were randomized to 2, 4, 6, and 10 mg/kg dose groups of six animals per group. High performance liquid chromatography method for determination of MBX in sheep plasma was used. Pharmacokinetic parameters were calculated by a non-compartmental method. The dose-normalized the area under the concentration-versus-time curve (AUC 0-∞ ) and dose-normalized maximum plasma concentration (C max ) in 10 mg/kg dose group were significantly higher than other dose groups. The elimination half-life (t 1/2λz ) of marbofloxacin in 10 mg/kg dose group was significantly longer than other dose groups. MBX exhibited dose-proportional pharmacokinetics and was well tolerated after 2, 4, 6 and 10 mg/kg doses in sheep. The 2, 4, 6, and 10 mg/kg doses of MBX could be administered in the treatment of infections caused by susceptible pathogens in sheep. However, additional studies are needed to identify whether MBX is efficient in sheep of naturally infected with susceptible bacteria.
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.
Pharmacokinetics of tolfenamic acid after different administration routes in geese (Anser cygnoides)
(2021-05-01) Turk E.; Tekeli I.O.; Durna Corum D.; Corum O.; Sakin F.; Uney K.
The pharmacokinetics and bioavailability of tolfenamic acid were determined in geese (Anser cygnoides) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral administrations at 2 mg/kg dose. In this study, eight healthy geese (3.5 ± 0.5 kg) were used. The study was performed in four periods according to a crossover design with a 15-day washout period between two administrations. The plasma concentrations of tolfenamic acid were analyzed using HPLC-UV, and pharmacokinetic parameters were calculated by noncompartmental analysis. The elimination half-life was 1.73, 2.51, 2.34, and 2.31 hr for IV, IM, SC, and oral routes, respectively. The volume of distribution at steady state and total clearance after IV administration were 0.25 L/kg and 0.16 L hr−1 kg−1, respectively. The peak plasma concentrations of tolfenamic acid after IM, SC, and oral administrations were 4.89, 2.94, and 2.92 μg/ml at 0.25, 0.75, and 1 hr, respectively. The bioavailability was 87.91, 77.87, and 76.03% for the IM, SC, and oral routes, respectively. Tolfenamic acid, which exhibits the good bioavailability and plasma concentration following IM, SC, and oral administrations at 2 mg/kg dose, may be useful in the treatment of inflammatory disease conditions in geese.
Pharmacokinetics of tolfenamic acid in goats after different administration routes
(2021-05-01) Turk E.; Tekeli I.O.; Durna Corum D.; Corum O.; Altinok Yipel F.; Ilhan A.; Emiroglu S.B.; Uguz H.; Uney K.
The aim of this study was to determine the pharmacokinetics and bioavailability of tolfenamic acid in goats after intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at 2 mg/kg dose. In this study, eight clinically healthy goats were used. The study comprised four periods, according to a crossover design with at least a 15-day washout period between treatments. Plasma concentrations of tolfenamic acid were determined by HPLC-UV, and the pharmacokinetic parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 1.60 h, 0.37 L/kg, and 0.27 L/h/kg, respectively. The mean peak plasma concentration following IM, SC, and PO administrations was 1.77, 1.22, and 0.30 μg/ml, respectively. The mean bioavailability following IM, SC, and PO administrations was 64.46, 55.43, and 19.46%, respectively. The PO route, which exhibits both the low plasma concentration and bioavailability, is not recommended in goats. The IV, IM, and SC routes, which show comparable pharmacokinetic profiles, may be proposed for use in goats. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in the goat.
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.