Disposition kinetics and tissue residues of tilmicosin following intravenous, subcutaneous, single and multiple oral dosing in geese (Anser anser domesticus).

Tilmicosin (TMC), a semi-synthetic macrolide antibiotic, is widely used in veterinary medicine due to its broad-spectrum, bacteriostatic properties. Frequently administered in various birds species, it is likely used off-label in geese as well. The study sought to investigate TMC's pharmacokinetics, tissue residues, in geese through in vivo experiments. The study involved longitudinal open studies on 15 healthy adult males, with three phases separated by one-month washout periods. Geese were administered TMC through intravenous (IV, 5 mg/kg), subcutaneous (SC, 10 mg/kg), and oral (PO, 25 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected for subsequent analysis at pre-assigned times. TMC in goose plasma was quantified by a fully validated HPLC method. Plasma concentrations were quantified up to 4 hr for the PO and IV routes, and up to 10 hr in the SC route. Significant variations in bioavailability were observed between SC (87%) and PO (4%) routes. The body extraction ratio was low at 0.03, suggesting minimal ability of the liver and kidneys to eliminate TMC. Multiple oral doses showed no plasma accumulation, but tissue data revealed extensive distribution and prolonged residence, up to 120 h, suggesting a sustained therapeutic effect despite the brief plasma half-life. Regarding the multiple PO doses, provisional withdrawal times of 6, 7.5, and 8 days were suggested for the liver, muscles, and kidneys, respectively, according to the MRL set for these matrices in chickens by EMA. In conclusion, while the practical oral administration is discouraged at the population level, SC administration of TMC may be appropriate for geese, albeit impractical for flock therapy.

Comparative pharmacokinetics of intravenous and subcutaneous pantoprazole in sheep and goats.

Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher Vd compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in Cmax and Tmax between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.

The effect of butyric acid and nucleotides supplementation on broiler (Gallus gallus domesticus) growth performance, immune status, intestinal histology, and serum parameters.

Background: Butyric acid and its derivatives support the immune system, lessen inflammation, and lessen oxidative stress in broilers in addition to preserving gut homeostasis and epithelial integrity. Broiler performance has also been demonstrated to rise with the addition of nucleotides to the diet. Aim: The purpose of the study was to ascertain the effects of butyric acid and nucleotides added to feed on the overall performance, immunity, oxidant/antioxidant enzyme levels, intestinal histology, and hepatic functions of broilers. Methods: Four experimental groups of thirty chickens, each were used in the present study. The groups were assigned as a control group that received normal diet without additives, butyrate (B) group received the diet supplemented with butyric acid (250 g/ton feed), nucleotides (N) group received the diet supplemented with nucleotides (200 g/ton feed), and the fourth group received the diet supplemented with a combination of butyrate and nucleotide (BN) (250 g/ton B feed, and 200 g/ton N feed, respectively). Necrotic enteritis was produced in ten birds from each group to assess the immune-modulatory effect of these supplements, antioxidant status, intestinal histology, and liver functions were measured in all experimental groups. Results: The addition of butyric acid and nucleotides to feed enhanced body weight, growth performance, hepatic functions, and antioxidant capabilities. Histological sections of the gut from challenged or unchallenged (with necrotic enteritis) groups in the BN group showed considerable improvement, as shown by strong proliferation in intestinal crypts and villus enterocytes. Conclusion: Nucleotides and butyric acid can be added to broiler feeding regimens to enhance growth and health.

A narrative review of the phenomenon of predatory journals to create awareness among researchers in veterinary medicine.

In recent years, especially since the COVID-19 pandemic, the number of predatory journals has increased significantly. Predatory journals exploit the "open-access model" by engaging in deceptive practices such as charging high publication fees without providing the expected quality and performing insufficient or no peer review. Such behaviors undermine the integrity of scientific research and can result in researchers having trouble identifying reputable publication opportunities, particularly early-career researchers who struggle to understand and establish the correct criteria for publication in reputable journals. Publishing in journals that do not fully cover the criteria for scientific publication is also an ethical issue. This review aimed to describe the characteristics of predatory journals, differentiate between reliable and predatory journals, investigate the reasons that lead researchers to publish in predatory journals, evaluate the negative impact of predatory publications on the scientific community, and explore future perspectives. The authors also provide some considerations for researchers (particularly early-career researchers) when selecting journals for publication, explaining the role of metrics, databases, and artificial intelligence in manuscript preparation, with a specific focus on and relevance to publication in veterinary medicine.

Comparative disposition kinetics of oral deracoxib in sheep and goats.

This study investigates the pharmacokinetics (PK) of deracoxib (DX), a selective COX-2 inhibitor, in sheep and goats following a single oral dose. DX, approved for dogs, holds potential as an alternative NSAID in small ruminants, particularly in light of heightened concern regarding abomasal ulceration. The study employed an oral administration of DX at a dose of 150 mg/head (sheep and goats), and plasma concentrations were determined after validating a high-performance liquid chromatography method, coupled to a UV detector. The PK parameters, including maximum plasma concentration (Cmax), time to reach Cmax (Tmax), elimination half-life (t1/2), and area under the curve (AUC), were evaluated through non-compartmental analysis. Results showed detectable DX in plasma up to 48 h, with no observed adverse effects. No significant differences in any PK parameters were noted between sheep and goats. Notably, t1/2 values were relatively long, at 16.66 h for sheep and 22.86 h for goats. Despite the fact that both species exhibited comparable drug exposure, high individual variability was noted within each species, suggesting to take into account individual variations in response to DX treatment, rather than species-specific considerations. Additional research involving pharmacodynamics and multiple-dose studies is warranted to comprehensively assess the profile of DX in these species.

Pharmacokinetic evaluation of oral deracoxib in geese (Anser anser domesticus).

The integration of pain management in veterinary practice, driven by heightened animal welfare concerns, extends to avian species where subtle and nonspecific behavioral signs pose challenges. Given that safety concerns with classical NSAIDs highlight the need for more targeted alternatives in birds, this study explores the pharmacokinetic (PK) properties of Deracoxib (DX), a COX-2 selective NSAID approved for use in dogs, following a single oral administration in geese. Six healthy female geese received 4 mg/kg DX. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma DX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software in a non-compartmental approach. The results indicated a terminal half-life of 6.3 h and a Tmax of 1 h, with no observed adverse effects. While refraining from claiming absolute safety based on a single dose, it is worth highlighting that further safety studies for DX in geese are warranted, suggesting a possibility for intermittent use. In addition, drawing conclusions on efficacy and suitability awaits further research, particularly in understanding COX-2 selectivity and protein binding characteristics specific to geese.

Risk of fibromyalgia in patients with primary muscle tension dysphonia: a possible local manifestation of a musculoskeletal systemic disorder.

OBJECTIVE: To investigate the risk of fibromyalgia in patients with primary muscle tension dysphonia. METHODS: A retrospective review was conducted of patients with primary muscle tension dysphonia, diagnosed based on history of dysphonia with evidence of laryngeal muscle tension on examination. Fibromyalgia was assessed using the Fibromyalgia Rapid Screening Tool ('FiRST'). RESULTS: Fifty patients were enrolled: 25 with primary muscle tension dysphonia (study group) and 25 matched controls. The mean age of the study group was 50.7 ± 15.2 years versus 49.5 ± 18.6 years for the controls, with a male to female ratio of 3:2 for both groups. Fifty-six per cent tested positive for fibromyalgia in the study group versus 4 per cent in the controls (p < 0.001). The mean Voice Handicap Index 10 score in the study group was significantly higher for those who screened positive for fibromyalgia compared to those who screened negative. There was a positive, strong point-biserial correlation between Fibromyalgia Rapid Screening Tool and Voice Handicap Index 10 scores (r = 0.39; p = 0.09). CONCLUSION: These results suggest that fibromyalgia is a significant co-morbid condition in primary muscle tension dysphonia.

Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese.

Tiamulin is an antibiotic approved exclusively in veterinary medicine, active against G-positive bacteria as well as Mycoplasma spp. and Leptospirae spp. The study was aimed to establish its pharmacokinetics and to evaluate drug effects on resistance in cloacal flora in vivo in geese. Eight healthy geese underwent to a two-phase longitudinal study (60 mg/kg single oral administration vs 60 mg/kg/day for 4 days) with a two-week wash-out period. Blood samples and cloacal swabs were collected at pre-assigned times. Minimal inhibitory concentration (MIC) has been evaluated for each isolated bacterial species. The pharmacokinetic parameters that significantly differed between the groups were Cmax (p = 0.024), AUC0-t (p = 0.031), AUC0-inf (p = 0.038), t1/2kel (p = 0.021), Cl/F (p = 0.036), and Vd/F (p = 0.012). Tiamulin exhibited a slow to moderate terminal half-life (3.13 h single; 2.62 h multiple) and a rapid absorption (1 h single; 0.5 h multiple) in geese, with an accumulation ratio of 1.8 after multiple doses. An in-silico simulation of multiple dosing did not reflect the results of the in vivo multiple dosage study. In both treatments, the MIC values were very high demonstrating a resistance (> 64 µg/ml) against tiamulin that can be present prior the drug administration for some strains, or emerge shortly after the commencing of treatment for some others.

Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations.

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.

Patient tolerance in office-based blue laser therapy for lesions of the vocal folds: Correlation with patients' characteristics, disease type and procedure-related factors.

Objective: To report patient tolerance in office-based blue laser therapy for vocal fold lesions. Methods: A retrospective review of the medical records of patients who underwent office-based blue laser therapy for lesions of the vocal folds between November 2021 and February 2023 was conducted. A total of 48 patients were included. Patient tolerance was assessed using the Iowa Satisfaction with Anesthesia Scale (IOWA). Patient tolerance was analyzed in relation to patients' demographic characteristics, disease type and severity, and procedure-related factors. Results: The mean tolerance score of the study group was 1.51 ± 1.1. There was a significant difference in the mean tolerance score between smokers and non-smokers (p = .038). Patients with vocal fold cyst (n = 3) had the highest mean tolerance score followed by patients with vocal fold polyps (n = 15). There was a nonsignificant difference in the mean tolerance score between benign lesions of the vocal folds and leukoplakia. Patients with lesions extending to more than half the vocal fold had less tolerance than those with lesions limited to less than half the vocal fold (1.91 vs. 1.27, p value .041). There was a moderate and significant negative correlation between vocal fold movement VAS, swallowing VAS, and tolerance score. The mean total duration of the procedures was 10.38 ± 4.8 min. There was a mild negative correlation between the duration of the procedure and tolerance. Conclusion: Office-based blue laser therapy for vocal fold lesions is a well-tolerated procedure. Patient should be instructed how to breathe quietly and avoid swallows to improve tolerance to surgery. Level of Evidence: 4.

Prevalence of Laryngeal Muscle Tension in Patients With Obstructive Sleep Apnea.

OBJECTIVE/HYPOTHESIS: To determine the prevalence of laryngeal muscle tension in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective case-control. METHODS: A total of 75 patients were included in this study. These were divided into a study group with a history of OSA (n = 45), and a control group with no history of OSA matched according to age and gender (n = 30). The risk of OSA was assessed using the STOP-BANG questionnaire. Demographic data included age, gender, body mass index, smoking, history of snoring, history of use of continuous positive airway pressure, and history of reflux disease. Symptoms such as hoarseness, throat clearing/cough, and globus sensation were also noted. The video recordings of the flexible nasopharyngoscopy of both groups were analyzed for the presence or absence of four laryngeal muscle tension patterns (MTPs). RESULTS: Twenty-five patients of the study group (55.6%) had signs of laryngeal muscle tension on laryngeal endoscopy compared to nine in the control patients (30%) (P = 0.029). The most common MTP observed in the study group was MTP III (n = 19), followed by MTP II (n = 17). Laryngeal muscle tension was more prevalent in patients of the intermediate and high-risk categories compared to those of the low-risk category (73.3% and 62.5% vs 28.6%, respectively) (P = 0.042). Patients with at least one MTP had more dysphonia and throat clearing than patients without any MTP. CONCLUSION: Patients with a history of OSA have a higher prevalence of laryngeal muscle tension in comparison to subjects with no history of OSA. Moreover, patients at high risk of OSA have a higher prevalence of laryngeal muscle tension than those at low risk of OSA.

Disposition kinetics of robenacoxib following intravenous and oral administration in geese (Anser anser domesticus).

Robenacoxib (RX) is a veterinary cyclooxygenase-2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four-month healthy female geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four-month washout period between the IV and the PO phases. Blood was collected 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, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 µg/mL at 0.50 h. The t1/2λz was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip-flop phenomenon. The Cl values corrected for the F% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4-month washout period. The absolute oral F% computed with the AUC method surpassed 150%, but after normalizing it to t1/2λz, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short t1/2λz.

Pharmacokinetics of robenacoxib following single intravenous, subcutaneous and oral administrations in Baladi goats (Capra hircus).

The purpose of this study was to assess the pharmacokinetics of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in goats after single intravenous (IV), subcutaneous (SC) and oral (PO) administrations. 5-month-old healthy female goats (n = 8) were used. The animals were subjected to a three-phase, two-dose (2 mg/kg IV, 4 mg/kg SC, PO) unblinded, parallel study design, with a four-month washout period between the IV and SC treatment, and a one-week period between the SC and PO treatment. Blood was drawn from the jugular vein in heparinized vacutainer tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10 and 24 h. Plasma RX concentrations were measured using HPLC coupled to a UV multiple wavelength detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non-compartmental approach. Following IV administration, terminal elimination half-life, volume of distribution and total clearance were 0.32 h, 0.24 L/kg and 0.52 L/h/kg, respectively. For SC and PO, the mean peak plasma concentrations were 2.34 and 3.34 µg/mL at 1.50 and 0.50 h, respectively. The t1/2λz was significantly different between the IV and the extravascular (EV) administrations (0.32 h IV vs 1.37 h SC and 1.63 h PO), suggesting the occurrence of a flip-flop phenomenon. The significant difference in Vd values between IV (0.24 L/kg) and EV (0.95 L/kg SC and 1.71 L/kg; corrected for F %) routes might have also triggered the t1/2λz difference. The absolute average SC and PO bioavailability were high (98% and 91%, respectively). In conclusion, the IV administration of RX might not be suitable for goats, due to its short t1/2λz. The EV routes, however, appear to be convenient for the drug's occasional use.

Intoxication of dogs and cats with common stimulating, hallucinogenic and dissociative recreational drugs.

Pets can have accidental, intentional, or malicious exposure to illicit drugs. It is a growing concern over the last decade because there is an increase in usage of illicit drugs in humans and diagnosis is difficult. Owners are often not aware of exposure, or they are reluctant to admit possession of recreational drugs in the household due to potential legal consequences. In addition, illicit drugs sold on the black market are often adulterated with other substances resulting in non-specific clinical presentation and aggravation of symptoms. There are affordable onsite diagnostic tests on the market which could facilitate diagnosis of intoxication with illicit drugs, but they give a lot of false positive results due to low specificity of the tests. In this paper we gathered information about the most common recreational drugs such as amphetamines, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), phencyclidine (PCP), lysergic acid diethylamide (LSD), psilocybin mushrooms and cocaine in terms of toxicokinetic properties, mechanism of toxic action, clinical presentation and treatment in dogs and cats.

Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses.

According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in the literature to quantify FX in biological fluids, using HPLC and LC-MS. FX presents remarkable pharmacokinetics and pharmacodynamics compared to other coxibs. It has an oral bioavailability of 80% or higher and is effectively absorbed by horses. Its volume of distribution is around 2 L/kg, and it is slowly eliminated. Due to the long elimination half-life (around 2 days), which allows a once daily dosing, a single 0.3 mg/kg loading dose has been recommended. This enables the establishment of steady-state drug concentrations within 24 h, making it appropriate for acute treatment as well. Its IC80 is equal to 103 ng/mL in whole blood and, with an EC50 of 27 ng/mL, it has the highest affinity for its receptor compared to the other commonly administered NSAIDs in horses.

Robenacoxib pharmacokinetics in sheep following oral, subcutaneous, and intravenous administration.

The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three-phase parallel study design with a washout period of 4 weeks, in which sheep received a 4 mg/kg SC dose in phase 1, a 4 mg/kg PO administration in phase 2, and a 2 mg/kg IV administration in phase 3. Plasma RX concentrations were measured over a 48 h period for each treatment using HPLC coupled to a UV multiple wavelength detector, and the PK 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 2.64 h, 0.077 L/kg, and 0.056 L/h kg, respectively. The mean peak plasma concentrations following SC and PO administrations were 7.04 and 3.01 µg/mL, respectively. The mean bioavailability following SC and PO administrations were 45.98% and 16.58%, respectively. The SC route may be proposed for use in sheep. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in sheep.