This study investigated age-related variations in the pharmacokinetics of enrofloxacin and its active metabolite, ciprofloxacin, in calves. This study was carried out on a total of 18 calves using a parallel pharmacokinetic design. Eighteen animals were assigned to three age groups, one, four, and eight months old, and received a single intravenous dose of 10 mg/kg enrofloxacin. Serial blood samples collected over 48 h were analyzed using high-performance liquid chromatography to determine plasma concentrations. In one-month-old calves, the pharmacokinetic parameters revealed a volume of distribution at steady state (Vdss) of 1.44 L/kg, total clearance (ClT) of 0.42 L/h/kg, elimination half-life (t1/2ʎz) of 2.52 h, and area under the concentration versus time curve (AUC0-last) of 23.36 h*μg/mL. Notably, the AUC0-last of enrofloxacin was increased and ClT decreased in the older age groups (four and eight months). Additionally, the Vdss of enrofloxacin significantly decreased in eight-month-old calves relative to younger groups, while t1/2ʎz showed statistically significant differences in the order of four months > eight months > one month. The conversion ratio of enrofloxacin to ciprofloxacin was highest in one-month-old calves (43.39%) and diminished in four-month-old (25.73%) and eight-month-old (23.04%) calves. The results indicated that the pharmacokinetics of enrofloxacin and ciprofloxacin at a dose of 10 mg/kg in cattle exhibited significant variation with age. However, pharmacokinetic/pharmacodynamic investigations in cattle of different ages are required to assess the impact of these pharmacokinetic alterations on clinical efficacy.

ABSTRACT Objective Tolfenamic acid (TA) is a non‐steroidal anti‐inflammatory drug that is commonly used in veterinary medicine. However, information on its pharmacokinetics in calves, particularly following subcutaneous (SC) administration, is limited. The aim of this study was to characterize the disposition of TA in calves following SC, intramuscular (IM) and intravenous (IV) administration. Methods Six calves received TA at a dose of 4 mg/kg via each route in a crossover design. Results TA exhibited route‐dependent pharmacokinetics. The terminal elimination half‐life increased significantly from IV (6.64 h) to IM (12.79 h) and SC (15.11 h) administration, which is consistent with flip‐flop kinetics following extravascular dosing. Following IV administration, the volume of distribution at steady state was moderate (0.67 L/kg), which suggests extensive plasma protein binding. The time to reach the maximum concentration was similar for the IM and SC routes. However, systemic exposure was markedly lower following SC administration, with peak plasma concentration, area under the curve and bioavailability being approximately half of those observed following IM injection. Plasma concentrations exceeded the EC50 values required to inhibit prostaglandin E2 and related inflammatory mediators for up to 24 h after IV administration and up to 48 h after IM or SC administration. Conclusions These findings demonstrate that SC administration of TA in calves results in prolonged but reduced systemic exposure compared with IM administration. The results support the need for route‐specific dosing considerations and provide a basis for further studies on residue depletion and determination of withdrawal period in food‐producing calves.

This study examined dose-dependent alterations in the pharmacokinetics of pentoxifylline (PTX) and its 5-hydroxyhexyl (M-I) metabolite in goats. Goats were administered PTX intravenously at doses of 10, 20, and 40 mg/kg. PTX and M-I plasma concentrations were quantified by HPLC. The t1/2ʎz values of PTX and its M-I showed significant differences between dose groups. The 40 mg/kg dose of PTX showed lower ClT and Vdss values compared to the 10 and 20 mg/kg doses. For PTX and M-I, higher dose-normalized AUC values were obtained at a dose of 40 mg/kg compared to other doses. Compared to other doses, high dose-normalized C0.08 was obtained for PTX at a dose of 40 mg/kg, and a low dose-normalized Cmax was obtained for M-I at a dose of 10 mg/kg. The AUC0-lastM-I/AUC0-lastPTX ratios were 8.9%, 9.6%, and 10.6% for dosages of 10, 20, and 40 mg/kg, respectively, with the maximum ratio observed at the highest dosage. The findings indicated that the pharmacokinetics of PTX and M-I at a dosage of 40 mg/kg exhibited considerable variability in goats. This information may be helpful in adjusting the dosage regimen of PTX in goats, but further studies are needed to determine dose-dependent therapeutic efficacy and safety.

The purpose of this study was to investigate the influence of injection site on danofloxacin pharmacokinetics in Pekin ducks. Thirty-two male Peking ducks were divided into 4 equal groups as intravenous (IV), pectoral muscles (IMP), thigh muscles (IMT) and subcutaneous (SC). Danofloxacin was administered to all groups at a dose of 10 mg/kg. Plasma concentrations of danofloxacin were quantified by HPLC-UV. The volume of distribution at steady state and total clearance values of danofloxacin after IV injections in ducks were 4.43 L/kg and 0.42 L/h/kg, respectively. The terminal elimination half-life (t1/2ʎz), area under the concentration-versus time curve (AUC)0-last, and peak plasma concentration (Cmax) were similar after SC and IMP injections of danofloxacin. However, t1/2ʎz was shorter and AUC0-last and Cmax were lower in the IMT group compared to the IMP group. The bioavailability was lower in the IMT group than in the IMP and SC groups. Danofloxacin exhibited similar pharmacokinetic profiles after SC and IMP injection into Pekin ducks. In the IMT group, pharmacokinetics altered significantly, resulting in reduced body exposure and residence time of danofloxacin. Optimizing the injection site to subcutaneous or pectoral muscle routes may improve danofloxacin's therapeutic efficacy in Pekin ducks, while caution should be applied with thigh muscle injections due to reduced bioavailability and systemic exposure.

The influence of the state of pregnancy (days 45, 90, and 135 of gestation) on the pharmacokinetics of levamisole was investigated in ewes. Twelve healthy Merino female sheep were allocated into two groups (n = 6 per group). The ewes in group 1 (non-pregnant) were not mated, while the ewes in group 2 (pregnant) were mated with rams by synchronizing their estrus cycles. Levamisole was injected intramuscularly once at a dose of 7.5 mg/kg into all ewes. Blood samples were taken at 13 different times over a 48-h period according to a defined protocol. Plasma samples were analyzed for levamisole via high-performance liquid chromatography. Pregnant ewes had significantly lower Cmax, AUC0-last, and t1/2ʎz of levamisole than non-pregnant ewes. There were no significant differences in Tmax between the two groups. The values of AUC0-last, Cmax, and t1/2ʎz decreased as pregnancy progressed. These results indicated that pregnancy reduced exposure (AUC0-last) and duration of levamisole presence in the body. This information contributes to the use of levamisole in pregnant ewes, but further studies are needed to determine the change in therapeutic effect related to pregnancy.

This investigation focuses on understanding the pharmacokinetic behavior of intravenously administered carprofen at doses of 0.7, 1.4, and 4 mg/kg in goats. Eighteen animals were randomly assigned into three groups, with six goats per group, and blood samples were collected at 22 time points post-administration. Plasma concentrations were analyzed using a validated HPLC-UV method, and key pharmacokinetic parameters were derived using non-compartmental analysis. Results show that, at 0.7 mg/kg, carprofen exhibited the total clearance (ClT) of 2.19 mL/h/kg, volume of distribution at steady state (Vdss) of 126.56 mL/kg, area under the curve (AUC0-last) of 321.00 h*µg/mL, and elimination half-life (t1/2ʎz) of 44.32 h. When comparing doses, an increase in ClT was observed at 4 mg/kg, and the volume of distribution increased at both 1.4 and 4 mg/kg dosages. Additionally, a reduction in dose-normalized AUC0-last was evident at the highest dose. Data showed that the effect of the drug may be prolonged as the dose increases. These differences between dose groups may be clinically insignificant after the single administration of all doses. Carprofen can be used at all three dose levels in goats; however, vigilance regarding the potential side effects and drug residues is essential, especially during repeated treatments.

This study aimed to examine the pharmacokinetic changes in tolfenamic acid administered intravenously and orally to ducks at different doses (2, 4, and 8 mg/kg). Furthermore, the binding ratio to plasma proteins was assessed utilizing the ultrafiltration method. Eighteen male Pekin ducks were randomly assigned to three dosage groups (2, 4, and 8 mg/kg), with each group undergoing a trial in two phases: intravenous (IV) and oral administration. The sample was analyzed using an approved HPLC-UV method. A non-compartmental analysis was utilized to evaluate the pharmacokinetic data. For 2 mg/kg IV injection, the area under the curve from zero to infinity (AUC0-∞), total clearance (ClT), volume of distribution at steady state (Vdss), and elimination half-life (t1/2ʎz) were 13.03 h*µg/mL, 0.15 L/h/kg, 0.30 L/kg, and 1.72 h, respectively. Following oral administration at a dose of 2 mg/kg, the AUC0-∞, peak plasma concentration (Cmax), and bioavailability were 6.32 h*µg/mL, 2.25 µg/mL, and 48.52%, respectively. The t1/2ʎz was extended, Cmax and AUC0-∞ elevated, Tmax shortened, and ClT decreased in a dose-dependent manner. No dose-related change was observed in Vdss and bioavailability. In ducks, tolfenamic acid’s plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated.

The objective of this investigation was to ascertain the impact of gender on the pharmacokinetics of meloxicam in sheep. The research was carried out on six female and six male Romanov sheep. Meloxicam was administered intravenously to sheep at a dose of 1 mg/kg. To determine the change in meloxicam concentration with time, blood samples were collected at 17 different time points up to 120 h after administration. Meloxicam concentrations in plasma samples were determined using high-performance liquid chromatography. The pharmacokinetics of meloxicam in sheep was found to differ according to gender. The values of total clearance (ClT), volume of distribution at steady state (Vdss), and elimination half-life (t1/2λz) of meloxicam in female sheep were 4.51 ± 0.56 mL/h/kg, 69.18 ± 6.68 mL/kg, and 11.96 ± 0.33 h, respectively. Compared to female sheep, ClT and Vdss were increased, and t1/2λz was decreased in male sheep. Plasma concentration and area under the curve of meloxicam were higher in female sheep. The findings of this study indicate that meloxicam's pharmacokinetics are not uniform across genders in Romanov sheep, with notable variations in plasma concentration, clearance, and half-life. These variations emphasize the importance of considering gender in the pharmacotherapy of sheep, potentially guiding clinicians in adjusting dosages for optimal therapeutic outcomes and maintaining food safety standards.

Danofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 ± 0.5 °C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t1/2ʎz), volume of distribution (Vdarea/F), total clearance (CL/F), peak concentration (Cmax), and area under the plasma concentration–time curve (AUC0–last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 µg/mL, and 82.46 h·µg/mL, respectively. Plasma t1/2ʎz, AUC0–last and Cmax increased concomitantly with trout growth, whereas CL/F and Vdarea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. Cmax and AUC0–last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 µg/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue.

Tilmicosin shows different degrees of cardiotoxic effect in various animal species depending on the route of administration and dose. We aimed to determine the effects of amiodarone and amiodarone+dobutamine treatments on tilmicosincardiotoxicity and survival time. 18 healthy goats were divided into tilmicosin, tilmicosin+amiodarone and tilmicosin+amiodarone+dobutamine groups. After drug administrations, the survival times of the animals in all groups were recorded. In addition, blood was drawn from the animals just before they died. Haemogram, troponin I, CK-MB, and other biochemical parameters were measured in all blood samples. Prolonged survival was observed in the treatment groups compared to the tilmicosin group. In the treatment groups, decreases in haemogram parameters, albumin, and total protein levels caused by tilmicosin could not be prevented, while the increase in troponin I level was prevented. In conclusion, while cardiotoxicity due to high troponin from tilmicosin was prevented, the survival rate was not affected in both treatment groups, and the survival time was extended at differing rates. In case of accidental or deliberate overdose of tilmicosin in animals, in addition to the use of amiodarone+dobutamine, the survival time may be prolonged, and the success may increase if the necessary symptomatic treatments and equipment support are available.

Flunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout (Oncorhynchus mykiss) maintained at 12 ± 0.6°C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High-pressure liquid chromatography-ultraviolet was employed to quantify flunixin concentrations. The elimination half-life (t1/2ʎz) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t1/2ʎz was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 ± 0.41 μg/mL at 4 h for oral administration and 13.98 ± 0.86 μg/mL at 2 h for IM administration. The in vitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 ± 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.

Bu çalışmanın amacı ördeklere tolfenamik asitin farklı dozlarda damar içi yolla uygulaması sonrası biyokimyasal parametrelerdeki değişimi ortaya koymaktır. Toplam 18 adet sağlıklı ördek 3 doz grubuna ayrıldı. Tolfenamik asit ördeklere 2 mg/kg, 4 mg/kg ve 8 mg/kg dozda damar içi yolla uygulandı. Kan örnekleri 0., 12., 24. ve 48. saatlerde brachial venden alındı. Kan örneklerinden elde edilen serumlardan kreatinin, üre, total protein, albümin, kolesterol, trigliserid, gamma glutamiltransferaz (GGT), alkalen fosfataz (ALP), alanin aminotransferaz (ALT) ve aspartat aminotransferaz (AST) seviyeleri otoanalizör cihazında belirlendi. Tolfenamik asitin artan dozlarda damar içi uygulaması ördekler tarafından iyi tolere edildi. Tolfenamik asitin farklı dozlardan uygulaması AST, ALP, GGT, albümin, total protein, kolesterol, üre ve kreatinin değerlerinde herhangi bir farklılığa neden olmadı (p>0.05). Tolfenamik asitin tüm dozları ALT ve trigliserid düzeylerinde önemli değişikliklere neden oldu (p

ABSTRACTThe aim of this study was to compare the pharmacokinetics of marbofloxacin after intravenous (IV) administration of a single dose of 10 mg/kg to calves of different ages. The study was carried on 1‐ (n = 6), 2‐ (n = 6), and 4‐month‐old (n = 6) Montofon calves. Plasma concentrations of marbofloxacin were measured using HPLC, and pharmacokinetic data were calculated by non‐compartmental analysis. The elimination half‐life (t 1/2ʎz ), volume of distribution at steady state (V dss), total clearance (ClT), and area under the concentration‐versus time curve (AUC0–∞) values of marbofloxacin in 1‐month‐old calves were 10.62 h, 1.03 L/kg, 0.08 L/h/kg, and 127.90 h*μg/mL, respectively. While the t 1/2ʎz (from 10.62 to 3.36 h) and AUC0–∞ (from 127.90 to 47.35 h*μg/mL) decreased in parallel with the age of the calves, ClT (from 0.08 to 0.21 L/h/kg) increased. The V dss of marbofloxacin was higher in 1‐ and 2‐month‐old calves compared to 4‐month‐old calves. After IV administration of marbofloxacin at a dose of 10 mg/kg, an ƒAUC0–24/MIC90 ratio of ≥ 125 was obtained for bacteria with MIC90 values of ≤ 0.60, ≤ 0.39 and ≤ 0.27 μg/mL in 1‐, 2‐, and 4‐month‐old calves, respectively. These results show that the antibacterial effect of marbofloxacin, which has concentration‐dependent activity, decreases due to age‐related pharmacokinetic changes and that the 10 mg/kg dose should be reviewed according to the MIC90 value of the bacteria.

This research aims to determine the effect of oral single-dose administration of 10, 50, and 100 mg/kg of enrofloxacin on ducks on biochemical parameters. The research was carried out on eighteen ducks. Ducks were divided into 3 equal groups to receive 10, 50, and 100 mg/kg doses. Blood samples were taken at 0, 6, 12, 24 and 48 hours. No clinical side effects were observed in ducks after enrofloxacin administration. When dose groups were compared, significant differences were observed in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), albumin (ALB), cholesterol (CHOL), total protein (TP) and creatinine (CRE) values (p<0.05). However, these differences returned to normal at the 48 hour. When the dose groups were evaluated within themselves, ALT, GGT, CHOL, triglyceride, and urea values did not differ (p>0.05). However, there were significant differences in AST, ALP, ALB, and CRE values at 10 mg/kg, AST at 50 mg/kg, and TP at 100 mg/kg (p<0.05). In conclusion, it was determined that oral administration of enrofloxacin to ducks at doses of 10, 50, and 100 mg/kg caused temporary changes in biochemical parameters. In this study, enrofloxacin was administered as a single dose. However, considering the repeated use of enrofloxacin in case of bacterial infection, attention should be paid to possible adverse effects that may occur in ducks.

Autism spectrum disorder is a neurodevelopmental disorder in which learning, communication, and social interaction are impaired. Research has sought to minimize the neural impairments associated with autism spectrum disorder and improve the quality of life. Recent studies suggest that boron may benefit nerve cells, with effects varying depending on the dosage. This study explored the impact of boron, administered as boric acid, on behavioral, biochemical, and histopathological parameters in a rat model of autism induced by propionic acid (PPA). Thirty-two male Sprague–Dawley rats were divided into control, autism model, and boron-treated groups. Behavioral tests were conducted pre- and post-PPA induction, with brain tissue analyzed post-euthanasia. Proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6)) and brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus. Histopathological evaluations were conducted on the hippocampus and cerebellum. Autism model rats displayed impaired learning, elevated BDNF and cytokine levels, microglial and astrocytic activation, and decreased Purkinje cell count. The boron-treated groups showed improvements, particularly with the 4 mg/kg dose. This dose enhanced learning and social interaction, reduced proinflammatory cytokine levels, prevented microglial and astrocytic activation, and increased Purkinje cell count. Boron treatment exhibited neuroprotective potential, ameliorating autism spectrum disorder deficits by modulating cytokines, BDNF, microglia, and astrocytes, with low doses yielding pronounced effects.

ABSTRACTObjectiveThis study aimed to investigate the plasma and milk pharmacokinetics, as well as the withdrawal time (WT) from milk of tolfenamic acid (2 and 4 mg/kg) following intravenous (IV) administration to eight healthy lactating Akkaraman sheep.MethodsThe trial was conducted in two periods in accordance with a crossover pharmacokinetic design. The concentrations of tolfenamic acid in the plasma and milk were determined using high‐pressure liquid chromatography and evaluated using non‐compartmental analysis. The WT of tolfenamic acid in milk was calculated using the WT 1.4 software.ResultsCompared to the 2 mg/kg dose, plasma volume of distribution at steady state (from 0.43 to 0.50 L/kg), terminal elimination half‐life (from 2.41 to 4.14 h) and dose‐normalized area under the plasma concentration–time curve (AUC0−∞, from 9.46 to 30.11 h µg/mL) increased, whereas total body clearance (from 0.21 to 0.13 L/h/kg) decreased at the 4 mg/kg dose. The peak milk concentration (Cmax) and AUC0−∞ values in milk were 0.26 µg/mL and 0.28 h µg/mL, respectively, for 2 mg/kg, and 0.43 µg/mL and 0.55 h µg/mL, respectively, for 4 mg/kg. Although the dose‐normalized Cmax of milk decreased depending on the dose, no difference was observed in dose‐normalized AUC0−∞. The AUC0−∞ milk/AUC0−∞ plasma ratio was 0.03 for 2 mg/kg and 0.02 for 4 mg/kg. The WT values calculated for milk at dosages of 2 and 4 mg/kg were 3 and 4 h, respectively.ConclusionsA decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians’ decision‐making processes.

Background: Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target- age animals Objective: To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods: The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC–UV and analyzed using a non-compartmental method. Results: ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t1/2ʎz and Vdss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC0-∞CIP/AUC0-∞ENR ratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion: The most important pharmacokinetic changes associated with aging in sheep are decreased Vdss and t1/2ʎz of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC0–24/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 μg/mL and for S. aureus (>30) with MIC of 0.5 μg/mL in all ages of sheep.

Carprofen can be used in the castration process of male goats due to its low side effects, long elimination half-life, and long-term effect. However, no studies were found on the pharmacokinetics and physiological efficacy of carprofen when employed for castration in male goats. The aim of this study was to determine the effect of xylazine (0.05 mg/kg, intramuscular) on the pharmacokinetics and physiological efficacy following intravenous administration of carprofen (4 mg/kg, intravenous) in male goat kids castrated using the burdizzo method. Thirty male Kilis goat kids (5-6 months and 18-30 kg of body weight) were randomly assigned to five groups (n = 6) as follows: healthy control (HC), castration control (CAST), castration+carprofen (CAST+CRP), castration+xylazine (CAST+XYL), and castration+xylazine+carprofen (CAST+XYL+CRP). Plasma concentrations of carprofen were analyzed via a non-compartmental method. Physiological parameters including serum cortisol, scrotal temperature, rectal temperature, and scrotal circumference were determined. Xylazine caused a decrease in the volume of distribution and clearance and an increase in the area under the curve of carprofen in CAST+XYL+CRP group (p < 0.05). The mean cortisol concentrations in CAST+CRP and CAST+XYL remained lower compared to CAST (p < 0.05). The mean cortisol concentrations in CAST+XYL+CRP were lower than in CAST+CRP and CAST+XYL (p < 0.05). In addition, the effect of carprofen administration alone on reducing the initial cortisol response to castration was observed from 6 to 48 h, while in combination with xylazine, it was observed immediately up to 48 h. No treatment differences were observed in rectal temperature, scrotal temperature, and scrotal circumference (p > 0.05). Xylazine caused an increase in plasma concentration and a decrease in clearance of carprofen after co-administration. However, when the effect of the combined administration of carprofen with xylazine on cortisol is evaluated, their combined use in castration process may be beneficial.

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.

OBJECTIVE:To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg-1 in Pekin ducks.STUDY DESIGN:Randomized experimental trial.ANIMALS:A total of 18 clinically healthy male Pekin ducks.METHODS:Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg-1) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.RESULTS:No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg-1 and 6.68 mL kg-1 hour-1, respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (Cmax), time to reach Cmax and bioavailability (p < 0.05).CONCLUSIONS AND CLINICAL RELEVANCE:Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.