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1.
The pharmacokinetics of monensin including apparent volume of distribution, total body clearance, systemic bioavailability, partition coefficients and tissue residues were determined in chickens. The drug was given by intravenous injection in the left wing vein at the dose of 0.46 mg/kg and by intracrop administration at the dose of 4 mg/kg according to a destructive sampling. The pharmacokinetic variables were compared after noncompartmental, naïve averaged, naïve pooled and nonlinear mixed-effects modelling analyses. Partition coefficients and tissue residues were determined after a treatment with feed additives (125 mg/kg of feed) of 33 days. The clearance, volume of distribution and bioavailabilty were approximately 2.2 L/h/kg, approximately 9 L/kg and approximately 30% respectively except with nonlinear mixed effects models that presented values of 1.77 L/h/kg, 14.05 L/kg and 11.36% respectively. Tissue/plasma partition coefficients were estimated to 0.83, 3.39 and 0.51 for liver, fat and thigh muscle respectively. Monensin residues after treatment were not detected 6 h after withdrawal except for fat where monensin was still quantifiable 12 h after. Pharmacokinetic variables seem to be inaccurate when assessed with non linear mixed-effects modelling associated to destructive sampling in chickens. Values varied slightly with noncompartmental, naïve averaged and naïve pooled analyses. The absorption, elimination and partition parameters will be incorporated into a physiologically based pharmacokinetic model and the depletion study will be used to test the ability of this model to describe monensin residues in edible tissues under different dosage regimens.  相似文献   

2.
Drug–drug interactions (DDIs) may adversely affect the prevention and cure of diseases. The effects of three polyether ionophore antibiotics, salinomycin (SAL), monensin (MON), and maduramycin (MAD) on the pharmacokinetics of florfenicol (FFC) were investigated in broilers. The chickens were fed rations with or without SAL (60 mg/kg feeds), MON (120 mg/kg feeds), or MAD (5 mg/kg feeds) for 14 consecutive days. FFC was given to the chickens either intravenously (i.v.) or orally (p.o.) at a single dose of 30 mg/kg body weight. Blood samples were taken from each chicken at 0–24 h postadministration of FFC. The plasma concentration of FFC was detected by high‐performance liquid chromatography. The plasma concentration of FFC decreased with i.v. or p.o. co‐administration of SAL, MON, or MAD in broilers, implying occurrence of DDIs during the co‐administration of FFC with these ionophores. Our findings suggest that more attention should be given to the use of FFC to treat bacterial infections in chickens supplemented with polyether ionophore antibiotics.  相似文献   

3.
1. The pharmacokinetics of monensin, including half‐life, apparent volume of distribution, total body clearance, systemic bio‐availability and tissue residues were determined in broiler chickens. The drug was given by intracrop and intravenous routes in a single dose of 40 mg/kg body weight.

2. Following intravenous injection the kinetic disposition of monensin followed a two compartments open model with absorption half life of 0.59 h, volume of distribution of 4.11 I/kg and total body clearance of 28.36 ml/kg/min. The highest serum concentrations of monensin were reached 0.5 h after intracrop dosage with an absorption half‐life of 0.27 h and an elimination half life of 2.11 h. The systemic bioavailability was 65.1% after intracorp administration. Serum protein‐binding tendency of monensin calculated in vitro was 22.8%.

3. Monensin concentrations in the serum and tissues of chickens after a single intracrop dose of pure monensin (40 mg/kg body weight) were higher than those after feeding a supplemented monensin pre‐mix (120 mg/kg) for 2 weeks. Monensin residues were detected in tested body tissues, collected 2, 4, 6 and 8 h after oral administration. The highest conentration was found in the liver. In addition, monensin residues were detected only in liver, kidney and fat 24 h after the last oral dose. No monensin residues could be detected in tissues after 48 h, except in liver which cleared completely by 72 h.  相似文献   


4.
Eimeria parasites were isolated from Nanhai Guangdong province (southern China) and studied in chickens in wire cages to evaluate their drug resistance against commonly used ionophores: monensin (100 mg/kg of feed), lasolacid (90 mg/kg), salinomycin (60 mg/kg), maduramicin (5 mg/kg) and semduramicin (25 mg/kg). Chinese Yellow Broiler Chickens were infected with 40,000 crude sporulated Eimeria oocysts at 15 days of age and prophylactic medication commenced a day prior to infection. Drug resistance was assessed for each ionophore drug by calculating the anticoccidial index (ACI) and percentage optimum anticoccidial activity (POAA) based on relative weight gain, rate of oocyst production and lesion values. Results revealed that Nanhai Eimeria oocysts comprising of E. tenella, E. maxima and E. acervulina, were resistant to monensin, sensitive to both salinomycin and lasolacid and partially sensitive to maduramicin and semduramicin. By selection for early development of oocysts during passage through chickens, the prepatent time of E. tenella, E. maxima and E. acervulina were reduced by 49, 36 and 22 h, respectively. The precocious lines are less pathogenic than the parent strains from which they were selected and conferred a satisfactory protection for chickens against coccidiosis. These ionophore-tolerant precocious lines could have wider applications in the development of anticoccidial vaccines for sustainable control of coccidiosis.  相似文献   

5.
Monensin and vitamin E concentrations, as well as histopathology of skeletal muscles and myocardium, were evaluated in broad-breasted white turkeys kept in commercial facilities. Turkeys with knockdown syndrome had myopathy of skeletal muscles, but no lesions in the myocardium. Generally, concentration of monensin in serum was highest in turkeys diagnosed with knockdown syndrome given more than 90 mg/kg of monensin in the diet, followed by turkeys diagnosed with knockdown syndrome given <90 mg/kg of monensin in the diet, healthy turkeys fed a diet that contained <90 mg/kg of monensin, and finally healthy turkeys fed a diet free of monensin (not detectable). However, the concentration of monensin was highly variable within each group, and the median was lower than the average. Vitamin E concentrations in the livers varied from low-normal to below normal and were statistically higher in healthy turkeys fed a diet free of monensin than in the livers of birds from the 3 groups exposed to monensin. This suggests that the concentration of monensin in serum positively correlates to the severity of clinical signs and pathology and to the amount of monensin in the feed. Although the methodology developed to detect serum monensin concentrations is beneficial and accurate for case investigations, it is recommended that several samples from each flock be evaluated because of variation within a flock. The current study also suggests that monensin in the feed could induce lower concentrations of vitamin E in the liver of turkeys and can predispose the turkeys to knockdown syndrome.  相似文献   

6.
The anticoccidial drugs narasin, lasalocid, monensin and salinomycin, with and without avoparcin, were fed to 1280 broiler chickens from 1 to 49 d old. At day 49 significant interactions were detected between avoparcin and the anticoccidial compounds for body weight and food consumption. This indicated that the increases in body weight and food consumption obtained with avoparcin were greater with some anticoccidial compounds (lasalocid and salinomycin for body weights and lasalocid for food consumption) than with others (monensin and narasin for body weights and monensin, narasin and salinomycin for food consumption). Overall there was evidence that avoparcin increased body weight (5.8%), food consumption (2.5%) and efficiency of food utilisation (2.9%). In addition avoparcin produced significant increases in plucked weight and the proportion of visceral fat together with and decreases in the proportions of edible giblets and waste offal.  相似文献   

7.
As a part of ongoing research to further elucidate frequent and species-specific causes of differences in oral bioavailability, a 3 mg/kg dose of racemic ketoprofen, a high permeability/low solubility compound in the human biopharmaceutics classification system, was administered intravenously and orally to different species. Due to possible enantioselective disposition kinetics and inversion, enantiomers were quantitated separately using a stereospecific HPLC assay. The absolute bioavailability of R(−) and S(+) ketoprofen in chickens, turkeys, dogs and pigs was 31.5% and 52.6%, 42.6% and 32.5%, 33.6% and 89.1%, and 85.9% and 83.5% respectively. Incomplete bioavailability in poultry is probably due to incomplete absorption in addition to first-pass elimination. Low bioavailability of R(−) ketoprofen in dogs, strongly indicates first-pass metabolism. High bioavailability of S(+) ketoprofen in dogs and both enantiomers in pigs confirms that absorption of these substances is complete and controlled by gastric emptying rather than dissolution.  相似文献   

8.
As a part of ongoing research to further elucidate frequent and species-specific causes of differences in oral bioavailability, a 3 mg/kg dose of racemic ketoprofen, a high permeability/low solubility compound in the human biopharmaceutics classification system, was administered intravenously and orally to different species. Due to possible enantioselective disposition kinetics and inversion, enantiomers were quantitated separately using a stereospecific HPLC assay. The absolute bioavailability of R(−) and S(+) ketoprofen in chickens, turkeys, dogs and pigs was 31.5% and 52.6%, 42.6% and 32.5%, 33.6% and 89.1%, and 85.9% and 83.5% respectively. Incomplete bioavailability in poultry is probably due to incomplete absorption in addition to first-pass elimination. Low bioavailability of R(−) ketoprofen in dogs, strongly indicates first-pass metabolism. High bioavailability of S(+) ketoprofen in dogs and both enantiomers in pigs confirms that absorption of these substances is complete and controlled by gastric emptying rather than dissolution.  相似文献   

9.
Healthy male turkeys not receiving monensin in their feed were treated with tiamulin by various methods and at different ages. Nine cycles of treatments were performed at the ages of 26, 40, 61, 89, 103, 117, 131, 145, and 160 days. Intramuscular of subcutaneous injections of 12.5 mg/kg tiamulin up to 145 days did not result in any signs of toxicity or impair growth rate. Administration at a dose of up to 25 mg/kg, using the drinking-water-deprivation technique, caused no effect in turkeys up to 160 days (marketing age).  相似文献   

10.
Healthy turkeys receiving 80 ppm monensin in their feed were injected at 26, 40 and 61 days of age with tiamulin at dosages of 12.5 and 25 mg/kg body weight. The aim of the study was to develop a regime for medicating with tiamulin turkeys receiving monensin in their feed, and which would circumvent the known toxicity created by the simultaneous administration of the two drugs. One injection of 12.5 mg/kg tiamulin up to the age of 61 days or 2 injections of 12.5 mg/kg tiamulin up to 40 days of age caused no mortality or adverse reaction.  相似文献   

11.
Sulfamethazine was administered to 8- to 10-week-old turkey poults intravenously (IV) at the dose level of 71.5 mg/kg of body weight, orally at the dose level of 143 mg/kg of body weight, or in the drinking water at the concentration of 0.1% over a 6-day period. The concentrations of free sulfamethazine in blood, muscle, skin, kidney, and liver were determined and semilogarithmic plots of concentration vs time for the various tissues indicated that the curve had a linear portion within the first 72-hour period of drug withdrawal. The rates of disappearance of sulfamethazine from the various tissues were proportional to the concentration in the tissues. After 72 hours of withdrawal and for as long as 14 days, sulfamethazine concentrations in kidney, liver, and skin of turkeys given the drug in the drinking water fluctuated between 0.1 and 0.4 ppm. Only 8.6% of the oral dose (143 mg/kg) and 16.5 to 17% of the IV dose (71.5 mg/kg) were recovered in urine and feces as the parent compound during the initial 72-hour period.  相似文献   

12.
Field observations suggest that coccidiosis is a common cause of death in broiler chicken flocks fed diets containing sufficient amounts of ionophore antibiotics (monensin, narasin, etc.) and contaminated with mycotoxins, particularly with T-2 fusariotoxin. To study this phenomenon, broiler chickens fed diets containing different amounts of T-2 toxin and free from monensin, or containing a preventive dose (100 mg/kg of feed) of monensin, were infected experimentally with coccidian oocysts. In all groups fed a diet containing monensin plus T-2 toxin severe clinical symptoms of coccidiosis (blood-stained faeces etc). occurred. Deaths and retarded growth depended on the toxin dose and were considerable. The body mass gain of chicks fed a diet containing monensin and T-2 toxin but not infected with coccidia was inferior to that of groups fed diets which contained either monensin or T-2 toxin (experiment 2). On the basis of these findings a negative interaction of the two compounds is assumed. This seems to be supported by the results of experiment 3, i. e. the finding that the lethal dose of narasin, a compound closely related to monensin both in chemical structure and mechanism of action, proved to be much lower (LD50 = 102 mg/kg body mass) for chickens fed a diet supplemented with T-2 toxin than for the control chickens (LD50 = 176 mg/kg body mass). The present results suggest that the feeding of diets severely contaminated with T-2 toxin may alter the anticoccidial efficacy of monensin.  相似文献   

13.
1. Disposition kinetics of doxycycline (doxy) was studied in healthy chickens and chickens experimentally intoxicated with aflatoxin B1 by intravenous, oral or intramuscular (i.m.) injection, in a single dose of 15 mg/kg body weight. In addition, the tissue distribution and residual pattern of the drug were determined in healthy and intoxicated chickens. 2. The maximum serum concentrations of doxy were reached 1.97 and 2.37 h after oral, and 1.57 and 2.92 h after i.m. dosage in healthy and aflatoxic birds, respectively. 3. The volumes of distribution and total body clearances were higher in aflatoxic birds (1.75 l/kg and 14.61 ml/kg/min) than in healthy chickens (0.93 l/kg and 4.6 ml/kg/min). Data relating to intravenous injection were analysed using a two-compartment open model curve fit. 4. Lower values of systemic bioavailability were observed in intoxicated birds (30.9 and 33.9%) than healthy ones (43.7 and 57.3%) after oral and i.m. administration, respectively. 5. The highest concentration of doxy residues were present in liver, kidney and serum followed by heart and muscles. Doxy residue concentrations in edible tissues was below the EEC limit 6 d after cessation of oral or i.m. medication with 15 mg/kg body weight twice daily for 5 successive days.  相似文献   

14.
The pharmacokinetics of kitasamycin after intravenous and oral administration in a dose of 300 mg/kg b.wt. was studied in 18 healthy and 18 Salmonella gallinarum naturally infected chickens. The tissue residue of the studied antibiotic was estimated in 36 normal chickens when it was given orally for 7 successive days. Therapeutic level of kitasamycin was achieved after 15 minutes and persisted for 20-22 hours after its oral administration. Higher serum kitasamycin concentrations were recorded in Salmonella gallinarum infected chickens. The elimination half-life of kitasamycin calculated after single intravenous injection was 9.03 hours in diseased chickens corresponding to 3.74 hours in healthy birds. The body clearance was significantly reduced in diseased chickens (23.86 ml/kg/min) when compared to that in normal ones (62.03 ml/kg/min). Kitasamycin treated broilers should not be slaughtered before 3 days from the last dose as it was detected only in bile and caecum at that time but not in edible tissues.  相似文献   

15.
Norfloxacin was administered orally to chickens and turkeys at 15 mg/kg body weight by pulse dosing at 24 h intervals and by continuous dosing at 100 mg/L in drinking water for five days. Blood samples were taken serially. Plasma norfloxacin concentrations were determined by high-performance liquid chromatography. The plasma norfloxacin concentrations increased slowly during continuous dosing and reached the MIC(90) (250 ng/mL) for Gram-negative pathogens by 12 h in chickens and 18 h in turkeys. The steady-state plasma concentration was attained in 36 h and remained at approximately 776.67+/-33.23 ng/mL in chickens and 682.50+/-28.55 ng/mL in turkeys. After pulse dosing, the plasma norfloxacin concentrations increased rapidly and exceeded the MIC(90) at 2 h in both species and remained above MIC(90) for 8 h in chickens and 6 h in turkeys. Pulse dosing provided half the steady-state concentration that was achieved by continuous dosing, 365.32+/-39.31 ng/mL in chickens and 306.03+/-32.26 ng/mL in turkeys, during the dosing interval of 24 h. Data for daily pulse dosing suggested that every administration corresponded to a single, daily repeated bolus administration although pulse dosing produced higher plasma concentrations more readily. Continuous and pulse dosing are both rational for the administration of norfloxacin to flocks of chickens and turkeys. We recommend that treatment be commenced with a pulse oral dose administered over a 4 h period and maintained by continuous oral medication for three to five consecutive days.  相似文献   

16.
A A Frank  W M Reed 《Avian diseases》1990,34(2):433-437
Coniine, an alkaloid of Conium maculatum (poison hemlock), was administered by gavage to immature chickens, quails, and turkeys at 0, 25, 50, and 100 mg/kg body weight. At 25 mg coniine/kg body weight, clinical signs were observed only in quails (2/10) and consisted of excitement, depression, hypermetria, seizures, opisthotonos, and flaccid paralysis. Chickens (9/10) and quails (8/10) dosed at 50 mg/kg body weight were affected, and several birds of each species died (2/10 and 5/10, respectively). Turkeys (7/10) were affected only when dosed at 100 mg/kg body weight, and quails (6/10), turkeys (4/10), and chickens (10/10) died at this dose. There were no gross or microscopic lesions. Coniine was detected in skeletal muscle and liver of birds dying after ingestion and was present in some survivors 7 days post-treatment.  相似文献   

17.
?ebkowska‐Wieruszewska, B.I., Kowalski, C.J. Sulfachlorpyrazine residues depletion in turkey edible tissues. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01147.x. Sulfachlorpyrazine (SCP) is currently used to treat coccidian infections in turkeys; however, there is no information available about the withdrawal period necessary for the turkey to be safe for human consumption. A high performance liquid chromatography method with ultraviolet‐visible light detection was adapted and validated for the determination of SCP in turkey tissues. The procedure is based on isolation of the (SCP sodium) compound from edible turkey tissues (muscles, liver, kidneys, and fat with skin) with satisfactory recovery (72.80 ± 1.40) and specificity. The residue depletion of SCP in turkeys was conducted after a dose of 50 mg/kg body weight/day had been administrated orally for 3 days. After treatment has been discontinued residue concentrations were detected in tissues on the 7th day. The highest SCP concentrations were measured in muscles. Based on the results presented in this study, it could be assumed that a withdrawal period of 21 days, before medicated turkeys could be slaughtered, would be sufficient to ensure consumer safety.  相似文献   

18.
Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the Cmax, Tmax, and t1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low‐dose group. The cTnI concentrations in the high‐dose group were 2.1 times that of cTnI in the low‐dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.  相似文献   

19.
Extensive studies have been conducted with monensin in target animals and laboratory animals to determine monensin concentrations in tissues, route of elimination, metabolism and pharmacokinetics of monensin. These studies indicate that monensin administered orally is absorbed, extensively metabolized, excreted in the bile and eliminated in the feces by the several species examined. Monensin did not accumulate in the tissues of orally dosed animals. When fed to cattle and chickens according to recommended practices, monensin was not detected (less than .05 ppm) in edible tissues. Environmental studies indicate that monensin is biodegradable in manure and soil.  相似文献   

20.
Salinomycin, a new ionophore antibiotic, was tested and compared with lasalocid and monensin for preventing experimentally induced lactic acidosis. Five rumen-fistulated adult cattle were used in a 5 X 5 Latin square design, and the treatments were as follows: no treatment (control), 0.11 mg of salinomycin/kg of body weight (S1), 0.22 mg of salinomycin/kg (S2), 0.66 of lasalocid/kg, and 0.66 mg of monensin/kg. Acidosis was induced by intraruminal administration of a ground corn-corn starch mixture (50:50, 12.5 g/kg) once a day for up to 4 days. Antibiotics were administered along with grain-starch mixture. Rumen and blood samples were obtained before and at 6, 12, and 24 hours after each carbohydrate-antibiotic dosing to monitor acid-base status. Control and S1-treated cattle became ruminally acidotic within 54 hours, whereas cattle treated with S2, lasalocid, and monensin resisted acidosis for up to 78 hours after dosing. Cattle treated with S2, lasalocid, or monensin had higher rumen pH and lower L(+)- and D(-)-lactate concentrations than did control or S1-treated cattle. Rumen pH decrease to below 5.0 in S2-, lasalocid-, and monensin-treated cattle was not due to lactic acid, but to increased production of volatile fatty acids. Rumen propionate proportion increased initially in antibiotic-treated cattle, but after 48 hours, butyrate proportion increased significantly. Despite low rumen pH and high lactate concentration, lacticacidemia was not evident, and the systemic acid-base disturbance was mild in control cattle.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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