Journal of veterinary pharmacology and therapeutics最新文献

We evaluated the effect of administration timing of meloxicam and robenacoxib on renal function, platelet cyclo-oxygenase and perioperative analgesia in 60 cats undergoing ovariohysterectomy, in a prospective randomized blinded controlled study. Twelve cats were randomly allocated to one subcutaneous treatment group: meloxicam (0.2 mg/kg) or robenacoxib (2 mg/kg) at admission (MA, RA), at induction (MI, RI) and robenacoxib at the end of surgery (RE). All cats received the same anaesthesia protocol. Plasma renin activity (PRA), plasma creatinine, drug concentrations and serum thromboxane (TxB₂) were measured sequentially. Anaesthesia significantly increased PRA, as activity at end of the surgery was higher than 2 h later (mean ± SD: 26.6 ± 2.8 versus 10.0 ± 3.9 ng/mL/h). PRA remained higher at 2 h post-surgery in admission groups compared to induction groups (p = .01). Serum TxB₂ was lower with meloxicam than robenacoxib (p = .001), and was lower in the MA than each robenacoxib group at catheter placement. Admission groups (16/24 from RA and MA groups) received earlier rescue analgesia than other groups (p = .033). In conclusion, the renin-angiotensin system was activated during anaesthesia despite cyclo-oxygenase inhibition, possibly due to hypotension or surgical stimulation. There was no effect of drug or timing on the markers of renal function but one cat receiving meloxicam at induction had suspected IRIS grade II acute kidney injury.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug approved to manage pyrexia associated with swine respiratory disease. In the United States, no analgesic drugs are approved for use in swine by the FDA, although they are needed to manage painful conditions. This study evaluated the pharmacokinetics and relative bioavailability of intranasal versus intramuscular flunixin in grower pigs. Six pigs received 2.2 mg/kg flunixin either intranasally via atomizer or intramuscularly before receiving flunixin via the opposite route following a 5-day washout period. Plasma samples were collected over 60 h and analysed using ultra-performance liquid chromatography and tandem mass spectrometry to detect flunixin plasma concentrations. A non-compartmental pharmacokinetic analysis was performed. The median C_max was 4.0 μg/mL and 2.7 μg/mL for intramuscular and intranasal administration, respectively, while the median AUC_inf was 6.9 h μg/mL for intramuscular administration and 4.9 h μg/mL for intranasal administration. For both routes, the median T_max was 0.2 h, and flunixin was detectable in some samples up to 60 h post-administration. Intranasal delivery had a relative bioavailability of 88.5%. These results suggest that intranasal flunixin has similar, although variable, pharmacokinetic parameters to the intramuscular route, making it a viable route of administration for use in grower swine.

There are two FDA-approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected immediately before a single dose of clodronate or saline and then on Days 1, 6, 28, 56 and 182 post-dose. mRNA was sequenced and analysed for differentially expressed transcripts. While no single transcripts were differentially expressed, pathway analysis revealed that p38 MAPK (p = .04) and Ras (p = .04) pathways were upregulated, and cadherin signalling (p = .02) was downregulated on Day 1. Previously investigated biomarkers, cathepsin K (CTSK) and type 5 acid phosphatase (ACP5), were analysed with RT-qPCR in a targeted gene approach, with no significant difference observed. A significant effect of time on gene expression for ACP5 (p = .03) and CTSK (p < .0001) was observed. Thus, these genes warrant further investigation for detecting clodronate use over time.

Enrofloxacin (ENR) residues in yellow catfish (Pelteobagrus fulvidraco) often exceed the standard due to excessive use. This study explored the pharmacokinetics of ENR and its metabolite ciprofloxacin (CIP) in yellow catfish following a single dose of 10 mg/kg body weight via intramuscular injection (IM), oral gavage (PO), or a 5-h drug bath at 10 mg/L and 25°C. High-performance liquid chromatography-mass spectrometry was used to determine the ENR and CIP concentrations in various tissues. The highest ENR concentration occurred with IM administration, peaking at 4.124 mg/L in the plasma, 8.359 mg/kg in the kidney, 6.272 mg/kg in the liver, and 5.192 mg/kg in the muscle. However, PO administration resulted in the longest metabolic time, with elimination half-lives of 56.47 h in plasma, 86.43 h in the kidney, 76.25 h in the liver, and 64.75 h in muscle. Additionally, the area under the concentration–time curve values for IM, PO, and bath administration in yellow catfish plasma were 108.36, 88.96, and 22.08 mg·h/L, respectively. These results indicate the effectiveness of all three administration methods in treating bacterial diseases in yellow catfish. The selection of an appropriate administration method depends on the minimal inhibitory concentration of ENR against pathogenic bacteria. Yellow catfish subjected to PO and IM administration require longer resting periods before they can be marketed than those receiving drug bath administration.

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone ‘RD0387’ (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg⁻¹ (A5); 7.5 mg kg⁻¹ (A7.5) and 10 mg kg⁻¹ (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed-breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one-way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal-Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p < .05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p = .033, p = .027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p = .005 and p = .003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p = .028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg⁻¹ resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs.

The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that V_dss decreased and C_0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 μg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.

Metronidazole (MTZ) is a 5-nitroimidazole anti-bacterial and anti-protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen-month old healthy male geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two-week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software with a non-compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 μg/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple-dose studies are necessary before its adoption in geese can be further considered.

This study aimed to evaluate the administration of doxycycline hyclate in a long-acting pharmaceutical preparation in pigs when administered either ad libitum as a feed medication or an oral bolus dose. In all instances, the studied dose was 20 mg/kg b.w. A total of 48 healthy crossbred, castrated male pigs (Landrace-Yorkshire) weighing 23 ± 4.3 kg were included in this trial. They were randomly assigned to six groups as follows: two groups for the experimental prototype 1 of doxycycline hyclate administering it ad libitum (Fad-lib) or as forced bolus (Fbolus); two groups for the experimental prototype 2 of doxycycline hyclate as for the former groups (FCad-lib and FCbolus), and two control groups receiving the same dose of doxycycline hyclate, but of a commercial premix, also as previously explained (Cbolus and Cad-lib). Statistical analysis of the mean pharmacokinetic values was carried out with Kruskal–Wallis and Dunn's tests. The relative bioavailability (Fr) of the best prototype, when administered ad libitum (FCad-lib), was five times larger than the reference group (Cadlib). These results allow the proposal that the referred differences achieved in the presented prototypes can mark a notable clinical difference, particularly in pathogens with some resistance.

Sedative as well as protective effects during hypoxia have been described for gamma-hydroxybutyric acid (GHB). Six swine (Sus scrofa domesticus) of 6 weeks old were administered NaGHB at a dose of 500 mg/kg intravenously (IV) and 500 and 750 mg/kg orally (PO) in a triple cross-over design. Repeated blood sampling was performed to allow pharmacokinetic analysis of GHB. Whole blood concentration at time point 0 after IV administration was 1727.21 ± 280.73 μg/mL, with a volume of distribution of 339.45 ± 51.41 mL/kg and clearance of 164.94 ± 47.05 mL/(kg h). The mean peak plasma concentrations after PO administration were 326.57 ± 36.70 and 488.01 ± 154.62 μg/mL for 500 mg/kg and 750 mg/kg, respectively. These were recorded at 1.42 ± 0.72 and 1.58 ± 0.58 h after PO dose for GHB 500 mg/kg and 750 mg/kg, respectively. The elimination half-life for IV and PO 500 mg/kg and PO 750 mg/kg dose was respectively 1.33 ± 0.30, 1.16 ± 0.31 and 1.11 ± 0.33 h. The bioavailability (F) for PO administration was 45%. No clinical adverse effects were observed after PO administration. Deep sleep was seen in one animal after IV administration, other animals showed head pressing and ataxia.

This study aimed to examine the depletion of tilmicosin residues in Gushi chickens following the administration at a concentration of 75 mg/L in their drinking water for three consecutive days. Plasma, liver, kidney, lung, muscle, and skin + fat samples were collected from 6 chickens at 6 h, 1, 3, 5, and 7 days after the treatment. Tilmicosin concentrations in the samples were determined using a high-performance liquid chromatography (HPLC) method. The findings revealed that the highest tilmicosin residues were detected in the liver, followed by the kidney, lung, skin + fat, muscle, and plasma. Notably, at 7 days post-treatment, no drug residue was detected in all samples except for the liver and kidney. The non-compartmental model was employed to calculate relevant pharmacokinetic parameters. The elimination half-lives (t_1/2λz) of tilmicosin were as follows, ranked from long to short: skin + fat (45.42 h), liver (44.17 h), kidney (40.06 h), plasma (37.64 h), lung (31.39 h), and muscle (30.05 h). Considering the current residue depletion and the maximum residue limits (MRLs) set by Chinese regulatory authorities, the withdrawal times for tilmicosin were estimated as 18.91, 10.81, and 8.58 days in the kidney, liver, and skin + fat, respectively. A rounded-up value of 19 days was selected as the conclusive withdrawal time. Furthermore, based on the observed tilmicosin concentrations in plasma and lung, combined with previously reported minimum inhibitory concentration (MIC) values against Mycoplasma gallisepticum, the current dosing regimen was deemed adequate for treating Mycoplasma gallisepticum infections in Gushi chickens.