64 research outputs found
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
Pharmacokinetics of a long-acting formulation of oxytetracycline in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at three different dosages
To date, the necessary pharmacokinetic information has been limited to establish suitable therapeutic plans for freshwater crocodiles. Therefore, this study was conducted to evaluate the pharmacokinetic profile of the oxytetracycline long-acting formulation (OTC-LA) in the freshwater crocodile, Crocodylus siamensis, following a single intramuscular (i.m.) administration at three different dosages of 5, 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 216 h after i.m. administration at the three different dosages. The plasma concentrations of OTC were measured using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. The Cmax (± SD) values of OTC were 2.15 ± 0.51 ”g/mL, 7.68 ± 1.08 ”g/mL and 17.08 ± 2.09 ”g/mL at doses of 5, 10 and 20 mg/kg b.w., respectively. The elimination half-life values were 33.59 ± 2.51 h, 38.42 ± 5.47 h and 38.04 ± 1.98 h at dosages of 5, 10 and 20 mg/kg b.w., respectively. Based on the pharmacokinetic data, the pharmacokinetic/pharmacodynamic (PK/PD) index, the susceptibility break-point and plasma protein binding, a dosage once every two weeks of 10 mg/kg b.w. OTC intramuscularly might be suitable for initiating the treatment of susceptible bacterial infections in freshwater crocodiles. However, further PK/PD studies are warranted to confirm whether the dose rates used in this study can produce longer-term antimicrobial success for diseases caused by susceptible bacteria in freshwater crocodiles
Pharmacokinetic profiles of the active metamizole metabolites in healthy horses
Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4-methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among other secondary metabolites, 4-aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 9 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC-UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0-last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0-last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54.
This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug
Pharmacokinetics of ivermectin after oral and intravenous administration in BiĆgorajska geese (Anser anser domesticus)
Aims To assess the pharmacokinetic profile of ivermectin in Bilgorajska geese (Anser anser domesticus) after single I/V or oral administration, in order to compare these routes of administration and assess oral bioavailability. Methods Ten healthy male geese were used in a single-dose, two-phase study with a 3-month washout period between phases. In the first phase, all geese were given 0.2 mg/kg I/V ivermectin, while in the second phase they were treated orally with the same dosage. Blood samples were collected at selected time points up to 480 hours after each administration. Samples were purified using protein precipitation and drug concentration was quantified using HPLC. The analytical method was validated on blank goose plasma and was characterised by an optimal linearity and a limit of quantification of 0.025 mu g/mL. The pharmacokinetic analysis was carried out using a non-compartmental approach. Results The drug was quantifiable up to 240 hours after I/V administration, while after oral treatment it was quantifiable up to 144 hours in most of the geese. The elimination half-life of ivermectin was approximately 3.8 (95% CI = 1.98-7.92; p = 0.027) times higher after I/V administration compared to oral administration. Moreover, the area under the curve from zero to the last detectable timepoint was 6.4 (95% CI = 4.65-8.74; p < 0.001) hours greater after I/V than oral administration. This difference led to a bioavailability of 20.38 (SD 5.92) %. Conclusions Following oral administration in geese, ivermectin has a bioavailability of approximately 20%. Further research on the action of ivermectin in the gastrointestinal tract is required along with assessment of tissue residues to allow calculation of withdrawal time to ensure consumer safety
T-2 toksin - pojavnost i toksiÄnost u peradi
T-2 toxin is the most toxic type A trichothecene mycotoxin. It is the secondary metabolite of the Fusarium fungi, and is common in grain and animal feed. Toxic effects have been shown both in experimental animals and in livestock. It has been implicated in several outbreaks of human mycotoxicoses. Toxic effects in poultry include inhibition of protein, DNA, and RNA synthesis, cytotoxicity, immunomodulation, cell lesions in the digestive tract, organs and skin, neural disturbances and low performance in poultry production (decreased weight gain, egg production, and hatchability). Concentrations of T-2 toxin in feed are usually low, and its immunosuppressive effects and secondary infections often make diagnosis difficult. If at the onset of the disease, a change in diet leads to health and performance improvements in animals, this may point to mycotoxin poisoning. Regular control of grain and feed samples is a valuable preventive measure, and it is accurate only if representative samples are tested. This article reviews the incidence and toxic effects of T-2 toxin in poultry.T-2 toksin je najtoksiÄniji predstavnik trikotecenskih mikotoksina tipa A. On je sekundarni produkt metabolizma plijesni roda Fusarium i Äesto je prisutan u ĆŸitaricama i hrani za ĆŸivotinje. Ć tetni uÄinci uoÄeni su u eksperimentalnih ĆŸivotinja i ĆŸivotinja u uzgoju. On se povezuje s pojavom bolesti ljudi od mikotoksikoza. UÄinci toksina u peradi su viĆĄestruki: inhibicija sinteze proteina, DNA i RNA, citotoksiÄni uÄinak, imunomodulatorni uÄinak, oĆĄteÄenje stanica probavnog sustava, organa i koĆŸe, ĆŸivÄani poremeÄaji te pad proizvodnih karakteristika u uzgoju peradi (slabiji prirast, pad nesivosti i valivosti). Koncentracije T-2 toksina u hrani redovito su vrlo malene, a zbog imunosupresivnog djelovanja toksina te istodobne sekundarne infekcije bolest se Äesto teĆĄko dijagnosticira. Pri pojavi bolesti promjenom hrane moĆŸe doÄi do poboljĆĄanja zdravstvenog stanja, ĆĄto tako|er upuÄuje na moguÄe trovanje mikotoksinima. Redovita kontrola uzoraka ĆŸitarica i hrane za ĆŸivotinje jedna je od preventivnih mjera, a detekcija mikotoksina u ĆŸitaricama i hrani pouzdana je samo ako se ispituje reprezentativan uzorak. U radu su opisani uÄestalost i toksiÄni uÄinci T-2 toksina u peradi
The mycotox charter: Increasing awareness of, and concerted action for, minimizing mycotoxin exposure worldwide
Mycotoxins are major food contaminants affecting global food security, especially in low and middle-income countries. The European Union (EU) funded project, MycoKey, focuses on âIntegrated and innovative key actions for mycotoxin management in the food and feed chainsâ and the right to safe food through mycotoxin management strategies and regulation, which are fundamental to minimizing the unequal access to safe and sufficient food worldwide. As part of the MycoKey project, a Mycotoxin Charter (charter.mycokey.eu) was launched to share the need for global harmonization of mycotoxin legislation and policies and to minimize human and animal exposure worldwide, with particular attention to less developed countries that lack effective legislation. This document is in response to a demand that has built through previous European Framework ProjectsâMycoGlobe and MycoRedâin the previous decade to control and reduce mycotoxin contamination worldwide. All suppliers, participants and beneficiaries of the food supply chain, for example, farmers, consumers, stakeholders, researchers, members of civil society and government and so forth, are invited to sign this charter and to support this initiative
Simultaneous determination of ergot alkaloids in swine and dairy feeds using ultra high-performance liquid chromatography-tandem mass spectrometry
Ergot alkaloids (EAs) are mycotoxins mainly produced by the fungus Claviceps purpurea. EAs are known to affect the nervous system and to be vasoconstrictors in humans and animals. This work presents recent advances in swine and dairy feeds regarding 11 major EAs, namely ergometrine, ergosine, ergotamine, ergocornine, ergocryptine, ergocristine, ergosinine, ergotaminine, ergocorni-nine, ergocryptinine, and ergocristinine. A reliable, sensitive, and accurate multiple mycotoxin method, based on extraction with a Mycosep 150 multifunctional column prior to analysis using UHPLC-MS/MS, was validated using samples of swine feed (100) and dairy feed (100) for the 11 targeted EAs. Based on the obtained validation results, this method showed good performance recovery and inter-day and intra-day precision that are in accordance with standard criteria to ensure reliable occurrence data on EA contaminants. More than 49% of the swine feed samples were contaminated with EAs, especially ergocryptine(-ine) (40%) and ergosine (-ine) and ergotamine (-ine) (37%). However, many of the 11 EAs were not detectable in any swine feed samples. In addition, there were contaminated (positive) dairy feed samples, especially for ergocryptine (-ine) (50%), ergosine (-ine) (48%), ergotamine (-ine), and ergocristine (-ine) (49%). The mycotoxin levels in the feed samples in this study almost complied with the European Union regulations
Simultaneous determination of multiple mycotoxins in swine, poultry and dairy feeds using ultra high performance liquid chromatography-tandem mass spectrometry
A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous determination of 17 mycotoxins in swine, poultry and dairy feeds using stable isotope dilution (13C-ISTD) and (ultra)-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A simple QuEChERS-based method (quick, easy, cheap, effective, rugged and safe) was developed consisting of soaking with a solution of 1% formic acid followed by extraction with acetonitrile, clean-up with C18 sorbent and finally adding 13C-ISTD before the UHPLC-MS/MS analysis. The chromatographic condition was optimized for separation and detection of the 17 mycotoxins using gradient elution. The methodâs performance complied with the SANTE/11813/2017 standard and had mean recovery accuracies in the range 70%â120% and precision testing of % relative standard deviation (RSD) †20%. The limit of detection and limit of quantification values ranged from 0.25 to 40.0 ng/g and 0.5 to 100.0 ng/g, respectively. Finally, the method was applied to analyze feed samples, with the results showing that fumonisins, zearalenone, aflatoxin B1 and deoxynivalenol were the most prevalent mycotoxins contaminating the feed samples
Pharmacokinetic profiles of clarithromycin in freshwater crocodiles (Crocodylus siamensis)
Clarithromycin (CLA) is a new ÎČ-lactamase-resistant macrolide antibiotic with potent activity against gram-positive and some gram-negative bacteria. To the authorsâ best knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for freshwater crocodiles. To assess the prudent use of antibiotic in reptiles, this study was conducted to explore the pharmacokinetic characteristics of CLA in the freshwater crocodile, Crocodylus siamensis, following either single intravenous (i.v.) or intramuscular (i.m.) administration at a dosage of 2.5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 h. CLA plasma samples were cleaned up using liquidâliquid extraction, and analysed by a validated liquid chromatography tandemâmass spectrometry (LC-MS/MS). CLA was quantifiable from 5 min to 72 h after i.v. administration, whereas it was detectable for 168 after i.m. administration at an identical dose rate. A non-compartmental model was used to fit the plasma concentration of CLA versus time curve for each crocodile. The t1/2λz value, similar for both routes (20 h), indicated that the overall rate of elimination of CLA in crocodiles is relatively slow. The average i.m. F% was complete. The protein plasma bound was found to be about 30%. CLA is a time-dependent antibiotic, and the T > MIC is the best PK/PD predictor for its efficacy. The CLA dosage of 2.5 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria
Disposition of a long-acting oxytetracycline formulation in Thai swamp buffaloes (Bubalus bubalis)
The present study aimed to characterize the pharmacokinetic profile of oxytetracycline long-acting formulation (OTC-LA) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 20 and 30 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 504 h. The plasma concentrations of OTC were measured by high-performance liquid chromatography (HPLC). The concentrations of OTC in the plasma were determined up to 264 h and 432 h after i.m. administration at doses of 20 and 30 mg/kg b.w., respectively. The Cmax values of OTC were 12.11 ± 1.87 Όg/mL and 12.27 ± 1.92 Όg/mL at doses of 20 and 30 mg/kg, respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were 52.00 ± 14.26 h and 66.80 ± 10.91 h at doses of 20 and 30 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK-PD index (T > MIC), i.m. administration of OTC at a dose of 30 mg/kg b.w once per week might be appropriate for the treatment of susceptible bacterial infection in Thai swamp buffaloes. 2016 John Wiley & Sons Ltd
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