Browsing by Author "Altan F."

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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.
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.
Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep
(2020-03-01) Altan F.; Corum O.; Yildiz R.; Eser Faki H.; Ider M.; Ok M.; Uney K.
In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t1/2β), total body clearance (ClT), volume of distribution at steady state (Vdss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h−1 kg−1, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.
Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves
(2019-11-01) Corum O.; Yildiz R.; Ider M.; Altan F.; Ok M.; Uney K.
The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr−1 kg−1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t1/2λz 4.74 and 3.62 hr, and AUC0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.
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 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 ceftriaxone following single ascending intravenous doses in sheep
(2018-12-01) Corum D.D.; Corum O.; Altan F.; Eser Faki H.; Bahcivan E.; Er A.; Uney K.
The objective of this study was to evaluate the pharmacokinetics of CTX following intravenous administration of ascending doses in sheep. In this study, six clinically healthy Akkaraman sheep (2.4 ± 0.4 years and 50 ± 3 kg of body weight) were used. CTX was administered intravenously to each sheep at 20, 40, and 80 mg/kg doses in a crossover design with a 15-day washout period. Plasma concentrations of CTX were measured using the high-performance liquid chromatography-UV method. Pharmacokinetic parameters were calculated by non-compartmental analysis. CTX was well tolerated following administration at 20, 40, and 80 mg/kg doses. The elimination half-life following administration of 40 and 80 mg/kg doses were significantly longer than that of 20 mg/kg dose (P < 0.05). The volume of distribution at steady state was similar among the groups (P > 0.05). When compared to 20 mg/kg, dose-normalized AUC0–∞ at the 80 mg/kg dose significantly increased (P < 0.05). The relation between dose and AUC0–∞ was linear. Our study showed that CTX can be used at 12-h intervals for 20, 40, and 80 mg/kg doses to maintain T > minimum inhibitory concentration (MIC) of >40% for the treatment of infections caused by bacteria with MIC values ≤2, ≤4, and ≤16 μg/mL, respectively. This information may be helpful in adjusting the dosage regimen, but there is a need for future work.
Pharmacokinetics of enrofloxacin and danofloxacin in premature calves
(2019-11-01) Corum O.; Altan F.; Yildiz R.; Ider M.; Ok M.; Uney K.
The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC0-48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr−1 kg−1, respectively. The PK parameters of ENR and DNX following IM injection were t1/2λz 21.10 and 28.41 hr, AUC0-48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC0-48CPR/AUC0-48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC0-24/minimum inhibitory concentration (MIC) and maximum concentration (Cmax)/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.
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 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.
The effects of Mannheimia haemolytica and albendazole on marbofloxacin pharmacokinetics in lambs
(2019-11-01) Altan F.; Sayin Ipek D.; Corum O.; Yesilmen Alp S.; Ipek P.; Uney K.
The study aimed to define the effects of M. haemolytica and a single oral dose of albendazole on the single-dose pharmacokinetics of marbofloxacin in lambs. The pharmacokinetic–pharmacodynamic integration of marbofloxacin was applied to describe a 3 mg/kg intramuscular dose in lambs. The 6 healthy and 12 naturally infected with M. haemolytica lambs (Akkaraman, males weighing 10–15 kg and aged 2–3 months) were used in this study. In the marbofloxacin group, 6 healthy lambs received marbofloxacin. In the albendazole group after 2 weeks washout period, the same animals received marbofloxacin on 1 h after albendazole. In the diseased marbofloxacin group, 6 lambs naturally infected with M. haemolytica received marbofloxacin. In the diseased albendazole group, 6 lambs naturally infected with M. haemolytica received marbofloxacin on 1 h after albendazole. The marbofloxacin and albendazole were administered each as a single dose of 3 mg/kg intramuscular and 7.5 mg/kg oral, respectively, in the respective groups. Plasma concentration of marbofloxacin was measured with HPLC-UV and pharmacokinetic parameters were analyzed by non-compartmental model. Albendazole did not change the pharmacokinetic profiles of marbofloxacin in healthy and diseased lambs. However, M. haemolytica affected the pharmacokinetics of marbofloxacin in diseased lambs, AUC0–24/MIC90 ratio was not found to be higher than 125, but Cmax/MIC90 ratios was found to be higher than 10 for an MIC value of 0.25 μg/mL in all groups. The marbofloxacin dose described in this study may not be effective for the treatment of infections due to M. haemolytica in lambs, with MIC ≤ 0.25 μg/mL.