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.

A smartphone-assisted photoelectrochemical POCT method via Z-scheme CuCo2S4/Fe3O4 for simultaneously detecting co-contamination with microplastics in food and the environment.

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.

Individual cytotoxicity of three major type A trichothecene, T-2, HT-2, and diacetoxyscirpenol in human Jurkat T cells.

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.

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 characteristics of florfenicol in green sea turtles (Chelonia mydas) and hawksbill sea turtles (Eretmochelys imbricata) after intramuscular administration.

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.

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.

Species Differences and Tissue Distribution of Heavy Metal Residues in Wild Birds.

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.

Disposition kinetics of meloxicam in green sea turtles (Chelonia mydas) after intravenous and intramuscular administrations.

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.

Pharmacokinetic disposition of marbofloxacin after intramuscular administration in estuarine crocodiles (Crocodylus porosus).

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.

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.

A New Benzaldehyde Derivative Exhibits Antiaflatoxigenic Activity against Aspergillus flavus.

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.

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.

Elution profiles of metronidazole from calcium sulfate beads.

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.

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.

Storage Fungi and Mycotoxins Associated with Rice Samples Commercialized in Thailand.

The study focused on the examination of the different fungal species isolated from commercial rice samples, applying conventional culture techniques, as well as different molecular and phylogenic analyses to confirm phenotypic identification. Additionally, the mycotoxin production and contamination were analyzed using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total, 40 rice samples were obtained covering rice berry, red jasmine rice, brown rice, germinated brown rice, and white rice. The blotting paper technique applied on the 5 different types of rice samples detected 4285 seed-borne fungal infections (26.8%) for 16,000 rice grains. Gross morphological data revealed that 19 fungal isolates belonged to the genera Penicillium/Talaromyces (18 of 90 isolates; 20%) and Aspergillus (72 of 90 isolates; 80%). To check their morphologies, molecular data (fungal sequence-based BLAST results and a phylogenetic tree of the combined ITS, BenA, CaM, and RPB2 datasets) confirmed the initial classification. The phylogenic analysis revealed that eight isolates belonged to P. citrinum and, additionally, one isolate each belonged to P. chermesinum, A. niger, A. fumigatus, and A. tubingensis. Furthermore, four isolates of T. pinophilus and one isolate of each taxon were identified as Talaromyces (T. radicus, T. purpureogenum, and T. islandicus). The results showed that A. niger and T. pinophilus were two commonly occurring fungal species in rice samples. After subculturing, ochratoxin A (OTA), generated by T. pinophilus code W3-04, was discovered using LC-MS/MS. In addition, the Fusarium toxin beauvericin was detected in one of the samples. Aflatoxin B1 or other mycotoxins, such as citrinin, trichothecenes, and fumonisins, were detected. These preliminary findings should provide valuable guidance for hazard analysis critical control point concepts used by commercial food suppliers, including the analysis of multiple mycotoxins. Based on the current findings, mycotoxin analyses should focus on A. niger toxins, including OTA and metabolites of T. pinophilus (recently considered a producer of emerging mycotoxins) to exclude health hazards related to the traditionally high consumption of rice by Thai people.

Comparative in vitro biotransformation of fipronil in domestic poultry using liver microsome.

Domestic poultry are among the non-target species of exposure to fipronil, but limited information is available on the metabolic effects of fipronil exposure in avian. We investigated the comparative capacity of in vitro biotransformation of fipronil among chicken, duck, quail, goose, and rat. Interspecies differences in kinetic parameters were observed; the clearance rate calculations (Vmax/Km) indicated that chicken and duck are more efficient in the cytochrome P450-mediated metabolism of fipronil to sulfone than quail, goose and rat. The lower hepatic clearance of fipronil in quail, goose and rat, suggested that fipronil sulfone may serve as a biomarker to indicate fipronil exposure in these species.

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.

Pharmacokinetic characteristics of azithromycin in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at three different dosages.

The study evaluated the pharmacokinetic features of azithromycin (AZM) in 15 freshwater crocodiles (Crocodylus siamensis) in Thailand. The crocodiles were administered a single intramuscular (i.m.) injection of AZM at three different dosages of 2.5, 5, and 10 mg/kg body weight (b.w.). Blood samples were collected at pre-assigned times up to 168 h. The plasma concentrations of AZM were measured using a validated liquid chromatography-tandem mass spectrometry method. The plasma concentration of AZM were quantifiable for up to 168 h after i.m. administration at the three different dosages. A non-compartmental model was used to fit the plasma concentration of AZM versus the time curve for each crocodile. The elimination half-life values of AZM were 33.70, 38.11, and 34.80 h following i.m. injection after dosages of 2.5, 5, and 10 mg/kg b.w., respectively. There were no significant differences among groups. The results indicated that the overall rate of elimination of AZM in freshwater crocodiles was relatively slow. The maximum concentration and area under the curve from zero to the last values of AZM increased in a dose-dependent fashion. The average binding percentage of AZM to plasma protein was 48.66%. Based on the pharmacokinetic data, the susceptibility break-point and the surrogate PK-PD index (T > MIC), the intramuscular administration of AZM at a dose of 10 mg/kg b.w. might be appropriate for the treatment of susceptible bacterial infections (MIC < 4 µg/ml) in freshwater crocodiles.