RESUMO

Colistin, also known as polymyxin E, is a member of the polymyxin group of antibiotics. It is approved in Europe to treat enteric infections caused by Gram-negative bacteria, such as Escherichia coli, in poultry, although the similarity of infections between species make it likely used off-label in geese as well.This study investigated the pharmacokinetics and tissue residues of colistin in geese through in vivo experiments. The study involved longitudinal open studies on 16 healthy adult male geese, divided into three phases separated by one-month washout period. Geese were administered colistin via intravenous (IV, 1 mg/kg), single oral (PO, 30 mg/kg), and multiple oral (SID, 2.5 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected at pre-assigned times for subsequent analysis. Colistin levels in geese plasma were quantified using a fully validated UHPLC-MS/MS method. Plasma concentrations could be quantified up to 24 h for the single PO (n= 2) and IV (n= 4) routes, and up to 10 h (n= 6) from the last dose administered for the multiple PO route (n=6). The bioavailability was significantly low, averaging 3 %. The terminal half-life in geese was 2.18 h following IV administration, similar to values found in other avian species. Following IV administration, clearance and volume of distribution values were 0.11 mL⋅h⁻¹â‹…g⁻¹ and 0.41 mL⋅g⁻¹, respectively. The body extraction ratio was low at 0.2 %, indicating minimal hepatic and renal elimination of colistin. Multiple oral doses showed no plasma accumulation, and tissue levels consistently remained below the maximum residue limit (MRL) set for food-producing animals. This study highlights the minimal systemic bioavailability and tissue penetration of colistin in geese, consistent with findings in other poultry and mammals. Future research should focus on intestinal colistin content in geese to optimize dosing strategies and minimize anti-microbial resistance.

RESUMO

Neonicotinoids, a neuro-effective class of insecticides, are heavily applied in agricultural activities worldwide. Poultry can be exposed to neonicotinoids by several routes, but the knowledge of neonicotinoid's metabolism in poultry and its associated interspecies differences is highly limited. Hence, this study aims to investigate the species differences in metabolite formations, as well as cytochrome P450 (CYP)-dependent metabolism of four major neonicotinoid compounds, acetamiprid, imidacloprid, clothianidin, and thiamethoxam, in poultry. In vitro biotransformation assays using hepatic microsomes of chicken, ducks, geese, quails, and rats were conducted. Metabolites of neonicotinoids were then screened by LC/Q-TOF and quantified by LC/MS/MS. The results revealed an existence of interspecies differences in the formations of N-[(6-chloro-3-pyridyl) methyl] -N-methyl acetamidine (IM-1-5) of acetamiprid and dm-clothianidin of clothianidin between chicken and other species. In addition, the greatest CYP activities in the metabolism of most neonicotinoid substrates, such as acetamiprid to dm-acetamiprid, imidacloprid to hydroxylated-imidacloprid and imidacloprid-olefin, clothianidin to dm-clothianidin, and thiamethoxam to clothianidin, were found in chicken. These results suggested that the CYPs in chicken may have a greater capacity for metabolism of neonicotinoids compared to other poultry. This study further revealed that the maximum intrinsic clearance of dn-imidacloprid and dn-clothianidin in ducks may be superintended by CYP-mediated nitro-reductions of imidacloprid and clothianidin. Further studies employing CYP recombinant enzymes may be required to elucidate the specific CYP isoforms that may be involved in neonicotinoid metabolism in avian species.

RESUMO

This study investigates the pharmacokinetics (PK) of montelukast (MTK), a cysteinyl leukotriene receptor antagonist increasingly being considered in veterinary medicine. In dogs, MTK has found indications mainly for treating atopic dermatitis as an off-label use. Six male Labrador dogs underwent a single oral administration of MTK (40 mg/dog) in both fasted and fed conditions according to an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was withdrawn to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 hr. MTK plasma concentrations were quantified using a validated HPLC method, and the data were analysed using PKanalix™ software with a non-compartmental approach. Concentrations remained quantifiable at 24 hr after administration, under both conditions. No significant differences were observed in the PK parameters between the fasted and fed states. MTK was relatively eliminated slowly, with t1/2 values of 8.10 and 7.68 hr after fasted and fed states, respectively. The attainment of maximum concentration (Cmax) occurred at a Tmax of 4 hr, with mean values of 1.98 µg/mL and 2.80 µg/mL under fasted and fed conditions, respectively. Given the unknown therapeutic range of MTK in dogs and the absence of controlled studies proving its efficacy in this species, further dosing adjustments and refinements should be considered based on both the current PK data and the need to establish an effective therapeutic range, if present. Future research should focus on efficacy studies, multiple-dose investigations, and pharmacodynamic assessments to evaluate the suitability of MTK use in dogs.

Assuntos

Acetatos , Estudos Cross-Over , Ciclopropanos , Jejum , Antagonistas de Leucotrienos , Quinolinas , Sulfetos , Animais , Cães , Sulfetos/farmacocinética , Sulfetos/administração & dosagem , Masculino , Quinolinas/farmacocinética , Quinolinas/administração & dosagem , Ciclopropanos/farmacocinética , Ciclopropanos/administração & dosagem , Acetatos/farmacocinética , Acetatos/administração & dosagem , Administração Oral , Antagonistas de Leucotrienos/farmacocinética , Antagonistas de Leucotrienos/administração & dosagem , Área Sob a Curva , Meia-Vida

RESUMO

IMPORTANCE: Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). OBJECTIVE: This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). METHODS: In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. RESULTS: The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 µg/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). CONCLUSIONS AND RELEVANCE: These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.

Assuntos

Peixes-Gato , Oxitetraciclina , Animais , Oxitetraciclina/farmacocinética , Oxitetraciclina/administração & dosagem , Oxitetraciclina/sangue , Administração Oral , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Injeções Intravenosas/veterinária , Meia-Vida

RESUMO

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.

RESUMO

As emerging contaminants, microplastics threaten food and environmental safety. Dibutyl phthalate (DBP, released from microplastics) and benzo[a]pyrene (BaP, adsorbed on microplastics) coexisted in food and the environment, harming human health, requesting a sensitive and simultaneous testing method to monitor. To address current sensitivity, simultaneousness, and on-site portability challenges during dual targets in complex matrixes, CuCo2S4/Fe3O4 nanoflower was designed to develop a smartphone-assisted photoelectrochemical point-of-care test (PEC POCT). The carrier transfer mechanism in CuCo2S4/Fe3O4 was proven via density functional theory calculation. Under optimal conditions, the PEC POCT showed low detection limits of 0.126, and 0.132 pg/mL, wide linearity of 0.001-500, and 0.0005-50 ng/mL for DBP and BaP, respectively. The smartphone-assisted PEC POCT demonstrated satisfied recoveries (80.00%-119.63%) in real samples. Coherent results were recorded by comparing the PEC POCT to GC-MS (DBP) and HPLC (BaP). This novel method provides a practical platform for simultaneous POCT for food safety and environment monitoring.

Assuntos

Técnicas Eletroquímicas , Contaminação de Alimentos , Microplásticos , Smartphone , Contaminação de Alimentos/análise , Microplásticos/análise , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Limite de Detecção , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Cobre/análise , Cobre/química , Benzo(a)pireno/análise , Dibutilftalato/análise

RESUMO

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.

Assuntos

Cabras , Pantoprazol , Animais , Masculino , Ovinos , Pantoprazol/farmacocinética , Pantoprazol/administração & dosagem , Injeções Subcutâneas/veterinária , Injeções Intravenosas/veterinária , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Meia-Vida

RESUMO

Mycotoxins are toxic, fungal secondary metabolites that contaminate agricultural commodities, food, and feed. Among them, T-2, HT-2, and diacetoxyscirpenol (DAS; the major type A trichothecene) are primarily produced from Fusarium species. These mycotoxins exert numerous toxicological effects in animals and humans, such as dermatotoxicity, haematotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, and immunotoxicity. In the present study, human Jurkat T cells were used as a model to investigate apoptotic cell death induced by T-2, HT-2, and DAS. The results showed that T-2, HT-2, and DAS decreased cell viability and increased production of Reactive Oxygen Species in a time- and dose-dependency. Based on their IC50 values, they could be ranked in decreasing order of cytotoxicity as T-2 > HT-2 > DAS. All tested mycotoxins caused DNA fragmentation, up-regulated cytochrome C, caspase 3, and caspase 9 mRNA levels, and down-regulated the relative expression of Bcl-2 and caspase 8. The effects of these trichothecenes on apoptosis were determined based on flow cytometry. At the IC50 concentrations, the percentages of apoptotic cells were significantly higher than for the controls. Taken together, these data suggested that T-2, HT-2, and DAS could induce apoptosis through the mitochondrial apoptotic pathway.

Assuntos

Apoptose , Sobrevivência Celular , Espécies Reativas de Oxigênio , Toxina T-2 , Tricotecenos , Humanos , Tricotecenos/toxicidade , Células Jurkat , Toxina T-2/toxicidade , Toxina T-2/análogos & derivados , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Citocromos c/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo

RESUMO

The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high-performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non-compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half-life was similar between the treatment groups (range 19-25 h), as well as the plasma protein binding (range 18.59%-20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 µg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles.

Assuntos

Antibacterianos , Tianfenicol , Tartarugas , Animais , Tartarugas/sangue , Tartarugas/metabolismo , Tianfenicol/análogos & derivados , Tianfenicol/farmacocinética , Tianfenicol/administração & dosagem , Tianfenicol/sangue , Injeções Intramusculares/veterinária , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Meia-Vida , Área Sob a Curva , Relação Dose-Resposta a Droga

RESUMO

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.

RESUMO

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.

Assuntos

Área Sob a Curva , Benzenossulfonamidas , Gansos , Animais , Feminino , Administração Oral , Meia-Vida , Sulfonamidas/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue

RESUMO

Birds are useful as bioindicators of metal pollution, but the variety of species and tissue distribution may influence the study of heavy metal burdens in birds. The objective of this study was to determine the levels of heavy metals in wild birds' carcasses to acquire information on species differences and the tissue distribution of metals in wild birds in Thailand. Species differences in metal buildup were observed in the livers and kidneys, but not in the feathers. A significantly higher accumulation of Cd was found in the livers and kidneys of the granivorous birds compared to those in the water birds. In all the groups of birds, the Pb level in the livers (>15 ppm) and feathers (>4 ppm) exceeded the threshold limits, causing potential lead poisoning and disturbing the reproductive success. The Cd accumulation in the kidneys was above 2-8 ppm, indicating increased environmental exposure to Cd in these birds. The Cd, Pb, Ni, Zn, and Fe concentrations in the livers could be estimated using the kidneys, while the Pb level in the liver may be predicted using feathers. Furthermore, water birds' feathers may be potentially appropriate bioindicators for long-term exposure. Research on the origin of metal contamination is needed to reduce the threat of heavy metals to the health of both birds and other wildlife species.

RESUMO

The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (Chelonia mydas), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre-assigned times up to 168 h. MLX in the plasma was cleaned-up and quantified using a validated high-performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non-compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half-life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (Cmax ) values of MLX were 1.05 µg/mL and 4.26 µg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half-life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (Chelonia mydas). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages.

Assuntos

Tartarugas , Animais , Meloxicam , Meia-Vida , Injeções Intramusculares/veterinária , Administração Intravenosa/veterinária

RESUMO

To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (Crocodylus porosus) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad-spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid-liquid extraction and analyzed using a validated high-performance liquid chromatography method with fluorescence detection. A non-compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half-life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC0-24 -to-MIC ratio >100-125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 µg/mL and 0.35 µg/mL, respectively.

Assuntos

Jacarés e Crocodilos , Animais , Área Sob a Curva , Injeções Intramusculares/veterinária , Fluoroquinolonas/farmacocinética

RESUMO

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.

RESUMO

Aflatoxin B1 (AFB1) is the most potent naturally occurring carcinogen for humans and animals produced by the common fungus Aspergillus flavus (A. flavus). Aflatoxin (AF) contamination in commodities is a global concern related to the safety of food and feed, and it also impacts the agricultural economy. In this study, we investigated the AFB1-inhibiting activity of a new benzaldehyde derivative, 2-[(2-methylpyridin-3-yl)oxy]benzaldehyde (MPOBA), on A. flavus. It was found that MPOBA inhibited the production of AFB1 by A. flavus, with an IC50 value of 0.55 mM. Moreover, the inhibition of conidiation was also observed at the same concentration. The addition of MPOBA resulted in decreased transcript levels of the aflR gene, which encodes a key regulatory protein for the biosynthesis of AF, and also decreased transcript levels of the global regulator genes veA and laeA. These results suggested that MPOBA has an effect on the regulatory mechanism of the development and differentiation of conidia, leading to the inhibition of AFB1 production. In addition, the cytotoxicity study showed that MPOBA had a very low cytotoxic effect on the Madin-Darby canine kidney (MDCK) cell line. Therefore, MPOBA may be a potential compound for developing practically effective agents to control AF contamination.

RESUMO

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.

RESUMO

BACKGROUND: Antibiotic beads are used to treat local bacterial infections by delivering high drug concentrations to infected tissue. OBJECTIVES: This study examined the elution characteristics of metronidazole from metronidazole-calcium sulfate (MCa) and metronidazole-calcium-potassium sulfate (MCaK) beads over 20 days and the antibacterial efficacy of the beads after storage. METHODS: The MCa and MCaK beads were prepared by mixing 250 mg of metronidazole and 10 g of calcium sulfate hemihydrate with water and a 3% potassium sulfate solution, respectively. The beads were placed in phosphate-buffered saline for the elution study. The metronidazole eluents were determined using high-performance liquid chromatography. The microstructures were examined by scanning electron microscopy (SEM), and the antimicrobial activity was evaluated by a microbioassay. RESULTS: For the 20-day study, the total amount of metronidazole released was greater in the MCa beads than in the MCaK beads by 6.61 ± 0.48 mg (89.11% ± 3.04%) and 4.65 ± 0.36 mg (73.11% ± 4.38%), respectively. The amounts of eluted drugs from the MCa and MCaK beads were higher than the minimum inhibitory concentration at 0.5 µg/mL against anaerobic bacteria at both 20 days and 14 days. SEM showed that calcium crystals on the outer surface had dissolved after elution, and thinner calcium crystals were prominent in the MCaK beads. The MCa and MCaK beads exhibited antibacterial activity after setting, followed by storage at room temperature or 4°C for 21 days. CONCLUSIONS: The MCa beads could release more drug than the MCaK beads, but all eluted metronidazole amounts were effective in controlling bacterial infections. Both metronidazole beads could be stored at ambient temperature or in a refrigerator.

Assuntos

Infecções Bacterianas , Metronidazol , Animais , Metronidazol/farmacologia , Sulfato de Cálcio/química , Cálcio , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Bacterianas/veterinária

RESUMO

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.

Assuntos

Anti-Inflamatórios não Esteroides , Gansos , Feminino , Gatos , Animais , Cães , Injeções Intravenosas/veterinária , Estudos Longitudinais , Anti-Inflamatórios não Esteroides/farmacocinética , Inibidores de Ciclo-Oxigenase 2 , Administração Oral

RESUMO

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.

Assuntos

Cabras , Feminino , Animais , Área Sob a Curva , Injeções Subcutâneas/veterinária , Administração Oral