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1.
建立了猪肝中阿苯哒唑及其代谢物阿苯哒唑砜、阿苯哒唑亚砜、2-氨基阿苯哒唑砜,噻苯哒唑及其代谢物5-羟基噻苯哒唑,甲苯哒唑及其代谢物氨基甲苯哒唑、5-羟基甲苯哒唑,芬苯哒唑及其代谢物芬苯哒唑砜、等效物奥芬哒唑,氟苯哒唑及其代谢物2-氨基-氟苯哒唑共14种苯并咪唑类药物及其代谢物残留检测的高效液相色谱-串联质谱方法。样品用乙酸乙酯提取,MCX固相萃取柱净化。WatersXterraC18色谱柱（2．1mm×150mm,5μm）分离,流动相A相为0．1％甲酸乙腈溶液;B相为0．1％甲酸水溶液,梯度洗脱,外标法定量。结果表明,14种苯并咪唑类药物及其代谢物标准溶液在10～1000ng／mL的浓度范围内呈现良好的线性关系,尺。均大于0．99,方法检测限为5斗g／kg,定量限为10μg／kg,14种苯并咪唑类药物及其代谢物在10—200μg／kg添加浓度范围内回收率均70％～120％之间。批内、批间相对标准偏差均小于20％。本方法灵敏、准确,满足食品安全检测法规的要求。  相似文献   

2.
Continued ingestion of plant secondary metabolites by ruminants can provoke pharmacological interactions with pharmaceutical agents used in animals. As some drugs and phytocompounds affect smooth muscle activity, the aim of this study was to verify the possible interaction between selected pharmaceutical agents and plant secondary metabolites towards bovine gastrointestinal motility. The interactions between phytocompounds—apigenin, quercetin, hederagenin, medicagenic acid—and medicines—erythromycin, flunixin meglumine and levamisole—were evaluated on bovine isolated abomasal and duodenal specimens obtained from routinely slaughtered cows. The obtained results confirmed the contractile effect of all three drugs used solely. Hederagenin and medicagenic acid (0.001 μM) enhanced the contractile effect of levamisole. Hederagenin additionally increased the impact of erythromycin. Both saponins (100 μM) showed synergistic effects with all tested pharmaceuticals. Apigenin and quercetin (0.001 μM) intensified the contractile response induced by erythromycin and levamisole. Moreover, both flavonoids (100 μM) showed an antagonistic interaction with all tested drugs which in that situation were devoid of the prokinetic effect. To conclude, plant metabolic metabolites such as saponins and flavonoids are potent modifiers of the effect of drugs towards gut motility. The synergy observed between phytocompounds and selected medicines can be beneficial in the treatment of cows with hypomotility disorders.  相似文献   

3.
Albendazole and fenbendazole are methylcarbamate benzimidazole anthelmintics extensively used to control gastrointestinal parasites in domestic animals. These parent compounds are metabolised to albendazole sulfoxide and fenbendazole sulfoxide (oxfendazole), respectively. Both sulfoxide derivatives are anthelmintically active and are manufactured for use in animals. They metabolites have an asymmetric centre on their chemical structures and two enantiomeric forms of each sulfoxide have been identified in plasma, tissues of parasite location and within target helminths. Both the flavin-monooxygenase and cytochrome P450 systems are involved in the enantioselective biotransformation of these anthelmintic compounds in ruminant species. A relevant progress on the understanding of the relationship among enantioselective metabolism and systemic availability of each enantiomeric form has been achieved. This article reviews the current knowledge on the pharmacological implications of the enantiomeric behaviour of albendazole sulfoxide and oxfendazole in domestic animals.  相似文献   

4.
The oxidative metabolism of fenbendazole: a comparative study   总被引：1，自引：0，他引：1  
The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ-SO), and p-hydroxyfenbendazole (FBZ-OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ-NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ-SO2), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ-OH and FBZ-SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25 degrees C and 37 degrees C incubation temperatures. The formation of the sulfone metabolite (FBZ-SO2), however, was practically nonexistent in catfish.  相似文献   

5.
Disposition of fenbendazole in the goat   总被引：1，自引：0，他引：1  
The disposition of fenbendazole was studied in goats after oral or IV administration. Plasma concentration vs time profiles were determined for fenbendazole and all of its metabolites. The total excretion of the drug and its metabolites in urine and feces was also measured for 6 days. A biliary cannula was inserted in 1 goat to study the excretion of fenbendazole and its metabolites into the bile. Fenbendazole was converted to its sulfoxide (oxfendazole), and the sulfone, primary amine, and p-hydroxylated metabolites. The active metabolite, oxfendazole, appeared in plasma, but only trace amounts were found in feces or urine. The major excretory metabolite was p-hydroxyfenbendazole.  相似文献   

6.
The in vitro biological oxidation of albendazole to its pharmacologically active sulfoxide and its sulfone by ovine liver microsomes has been studied. Sulfoxidation (maximal rate = 0.412 nmole/min/mg of protein, Michaelis constant = 185 X 10(-6) M) was 107 times more potent than formation of albendazole sulfone. The sulfoxidation corresponds to a reduced nicotinamide-adenine dinucleotide phosphate-dependent enzymatic system characterized by a pH optima value around 8. Flavin adenine dinucleotide-containing monooxygenase could be responsible for this S-oxygenation because of the strong inhibitory effect of methimazole. Albendazole sulfoxidase is inhibited competitively by the related anthelmintic drug fenbendazole (inhibitory constant = 243 X 10(-6) M) and noncompetitively by chlorpromazine (inhibitory constant = 135 X 10(-6) M). At high concentration, chloramphenicol, erythromycin, nalidixic acid, and hexobarbital are less active inhibitors, whereas dexamethasone acetate significantly enhances the reaction which is not inhibited by either carbon monoxide, griseofulvin, imidazole, phenylbutazone, or proadifen.  相似文献   

7.
The effect of ruminal flora on the disposition of benzimidazole anthelmintic drugs was studied in dual-flow continuous-culture fermenters (artificial rumens). Six 1,320-mL artificial rumens were inoculated with ruminal fluid and fermentation conditions were maintained constant at 39 degrees C, pH 6.4, solid dilution rate of 5%/h, and liquid dilution rate of 10%/h to simulate standard ruminal fermentation conditions. The study was repeated in two consecutive periods. Two hours after the inoculation of rumen fluid, the fermenters were fed 30 g of a 60:40 forage:concentrate ration. Within each period two fermenters per treatment were immediately dosed with 104 mg of netobimin, 52 mg of albendazole, or 39 mg of albendazole sulfoxide. Concentrations of netobimin, albendazole, albendazole sulfoxide and its enantiomers, and albendazole sulfone were analyzed by high performance liquid chromatography at 0.25, 0.5, 1, 2, 4, 6, and 8 h after dosage. Reductive metabolism by the ruminal bacteria was observed, favoring the production of albendazole, the most potent anthelmintic molecule. No differences in the production or consumption of albendazole sulfoxide enantiomers were observed, indicating that the ruminal bacteria metabolism was not enantioselective. Because benzimidazole anthelmintic drugs are generally administered orally, the ruminal flora play an important role in the bioavailability of these drugs. In our study, increased concentrations of albendazole in the three treatments, due to reductive ruminal biotransformation, suggests that ruminal biotransformation may improve the efficacy of orally administered netobimin, albendazole, and albendazole sulfoxide.  相似文献   

8.
Five adult Saanen goats were dosed orally 3 times with albendazole (2.5 mg/kg of body weight) at 24-hour intervals, and blood samples were taken by jugular venapuncture at standardized intervals. Plasma was analyzed to determine concentrations of S-oxidation metabolites, and a chiral column was used for enantiomeric discrimination of the sulfoxide metabolite of albendazole. Marked changes were evident between the first and subsequent plasma profiles concerning, on one hand, the proportions of sulfoxide and sulfone metabolites concentrations and, on the other hand, the enantiomeric balance of sulfoxide metabolite. These correlated phenomena may be explained by the following arguments: the enzyme responsible for sulfoxidation is mainly a flavine-containing monooxygenase, whereas the enzyme responsible for sulfonation is a cytochrome-dependent monooxygenase; the latter, but not the former, is induced by albendazole; the enantioselectivities of both enzymic systems are opposite, the flavine produces the (+) sulfoxide, whereas the cytochromes can use as a substrate, specifically, the (-) sulfoxide.  相似文献   

9.
The anthelmintic efficacy of benzimidazoles (albendazole, fenbendazole and oxfendazole), levamisole, oral ivermectin and closantel was evaluated on a farm in Kenya using faecal egg count reduction test, larval cultures and a controlled slaughter trial. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles, levamisole and ivermectin, and of Trichostrongylus colubriformis and Oesophagostomum spp. against levamisole on the same farm. Ivermectin resistance developed to 47% within 15 months of first use. Closantel was effective against the benzimidazoles, levamisole and ivermectin resistant H. contortus.  相似文献   

10.
Plasma concentrations of anthelmintics and their metabolites were determined after cattle were treated at recommended dose rates and routes of administration. Fenbendazole, oxfendazole, febantel, albendazole and thiabendazole were given orally and oxfendazole was also administered with an intraruminal injector. After fenbendazole, oxfendazole and febantel were administered, fenbendazole, oxfendazole and fenbendazole sulphone were all detected in plasma in each case. However, there were marked differences between the three anthelmintics in the peak concentrations and areas under the plasma concentration/time curve (AUC) of these three metabolites. Intraruminal administration of oxfendazole produced higher AUC for fenbendazole and fenbendazole sulphone than did oral administration. Albendazole sulphoxide and sulphone were detected in cattle plasma after albendazole administration but no parent drug was present. These metabolites disappeared more rapidly in cattle than has been reported for sheep. Only 5(6)hydroxythiabendazole was detected in cattle plasma after thiabendazole treatment.  相似文献   

11.
Disposition of fenbendazole in cattle   总被引：1，自引：0，他引：1  
Fenbendazole (FBZ) was administered to cattle IV and orally in a crossover design. Plasma concentration vs time profiles were reported for FBZ and its major metabolites, the sulfoxide (oxfendazole) and the sulfone. The total excretion of FBZ and its metabolites in urine and feces was also measured for 6 days after administration. All known metabolites were identified in urine and feces except for fenbendazole amine. Neither this minor metabolite nor p-hydroxyfenbendazole (FBZ-OH) appeared in plasma. The major excretory product was FBZ-OH. After oral administration, only 44.6% of the dose was eliminated after 6 days, indicating a fairly high degree of sequestration, probably within the gastrointestinal tract.  相似文献   

12.
Multiple resistance to benzimidazoles (fenbendazole, albendazole and mebendazole) in a strain of Haemonchus contortus in sheep was detected on a farm where fenbendazole resistance had already been identified. Following a faecal egg count reduction test, this was confirmed by both critical and controlled anthelmintic tests. Different groups of sheep infected naturally or given an experimental infection with the fenbendazole-resistant strain were treated with the recommended doses of various anthelmintics. Compared to the control group, percentage reductions in faecal egg counts of sheep treated with fenbendazole, albendazole, mebendazole, levamisole and morantel varied between 56% and 81% and worm counts between 71% and 86%. The results indicate the presence of multiple anthelmintic resistance in this strain of H. contortus on this farm. Sheep treated with ivermectin and closantel showed 100% reductions in faecal egg and worm counts, suggesting high efficacy of these drugs against the population of H. contortus on this farm.  相似文献   

13.
In the present study the bioavailability of febantel paste and febantel suspension was investigated in the fully hydrated and the dehydrated camel. The serum concentrations of febantel and its metabolites, fenbendazole, oxfendazole and fenbendazole sulfone were determined by high performance liquid chromatography following extraction with ether. The exposure to febantel and its metabolites in fully hydrated camels was significantly higher in camels dosed with febantel paste compared to febantel suspension, as measured by AUC and C max· The AUC and C max of fenbendazole and oxfendazole were significantly lower in dehydrated camels as compared to control camels dosed with febantel paste. The systemic availability of febantel suspension in control and dehydrated camels was very low and differences between dehydration and control phases were insignificant. The low systemic availability of febantel in camels dosed with febantel suspension may cause nematodes to become resistant to this anthelmintic. It is, thus, suggested to increase the dose of febantel paste in dehydrated camels in order to increase the exposure to febantel and its metabolites. The binding of febantel, fenbendazole, oxfendazole and fenbendazole sulfone to camels'serum proteins was over 85%. Oxfendazole was only about 70% bound. Dehydration of 10 days did not affect the binding of these benzimidazole derivatives to serum proteins.  相似文献   

14.
Effects of praziquantel (PZQ), levamisole (LEV), mebendazole (MBZ), fenbendazole (FBZ) and albendazole (ABZ) on the lactate dehydrogenase (LDH) activity of Cotylophoron cotylophorum were studied in vitro. Maximum levels of inhibition of LDH catalysing both oxidation and reduction reactions were observed in PZQ- and LEV-treated worms. Similarly, benzimidazoles - MBZ, FBZ and ABZ - have also significantly inhibited the activity of LDH catalysing the oxidation of lactate; whereas the activity of LDH catalysing the reduction of pyruvate was accelerated. This affects the mitochondrial energy generating process which ultimately proves fatal to the parasite. Therefore, the mode of action of benzimidazoles is primarily on the activation of LDH catalysing the conversion of pyruvate to lactate.  相似文献   

15.
Tubulin was estimated to account for 0.3% of the total soluble protein in Trichinella spiralis cytosolic fractions. Tubulin from T. spiralis was partially purified by precipitation with either taxol or vinblastine sulphate. Immunoblotting with alpha- and beta-tubulin monoclonal antibodies revealed the presence of tubulin in T. spiralis partially purified preparations. Electrophoretic mobility of T. spiralis tubulin in sodium dodecyl sulphate-polyacrylamide gels was very similar to that shown by pig brain tubulin. Further studies with colchicine binding assays indicated that T. spiralis tubulin has binding features similar to that of tubulin from other nematodes: colchicine association constant = 8.1 x 10(-4) M and competitive inhibition of colchicine binding by podophyllotoxin, with an inhibition constant of 1.3 x 10(-6) M. Finally, inhibition of colchicine binding by several benzimidazoles (mebendazole, fenbendazole, oxibendazole and albendazole) was investigated. All the benzimidazoles inhibited colchicine binding in a competitive manner, with inhibition constant values ranging from 1.4 x 10(-7) M (mebendazole) to 3.9 x 10(-6) M (fenbendazole).  相似文献   

16.
Calves were given albendazole (ABZ) daily in feed at levels of 0,3 or 5 mg kg?1 day?1. None of the ABZ treatment levels was significantly effective in reducing Fasciola hepatica burdens. A dose rate of 5 mg kg?1 day?1 did significantly reduce the fecal egg count. Measurements of serum druf levels from calves following a single dose of ABZ showed ABZ levels to be low, but sulfoxide and sulfone metabolites of ABZ were present in (significant) larger quantities. The total available sulfoxide present in calves, however, was much lower than in sheep receiving the same dose of ABZ. Measurements of serum metabolite levels from sheep and calves which were given daily low-level doses of ABZ also indicated that the seum sulfoxide levels of calves were much lower than those of sheep receiving tha same ABZ dose. The results indicated that ABZ is not an effective prophylactic treatment for bovine fascioliasis and the differences in efficacy between sheep and cattle correlated with the differences in serum metabolites levels.  相似文献   

17.
Adult mouflon ewes (Ovis musimon) were treated repeatedly with therapeutic doses of albendazole (ABZ, p.o. 7.5 mg/kg of body weight/day, for five consecutive days). Animals (treated or control) were sacrificed 24 h after the fifth dose of ABZ and liver and small intestine were collected to prepare microsomes. The activities of several biotransformation enzymes were measured in both hepatic and intestinal microsomes. A significant increase in the activity and amount of cytochromes P4501A (CYP1A) was observed in both tissues of ABZ treated mouflons compared to control animals. No other biotransformation enzymes tested were affected by five ABZ doses. The in vitro biotransformation of ABZ was studied in hepatic and intestinal microsomes from ABZ treated and control mouflons. Concentrations of two main ABZ metabolites - pharmacologically active ABZ sulfoxide and pharmacologically inactive ABZ sulfone were analysed using HPLC. A significant increase in rate of formation of ABZ sulfone (which is catalysed by CYP1A) was observed in hepatic as well as in intestinal microsomes from ABZ treated animals. The enhancement of ABZ deactivation by its repeated administration may affect the anthelmintic efficacy of this drug and may contribute to the development of parasite resistance.  相似文献   

18.
Pharmacokinetic behaviour of fenbendazole in buffalo and cattle   总被引：1，自引：0，他引：1  
Sanyal, P.K. Pharmacokinetic behaviour of fenbendazole in buffalo and cattle. J. vet. Pharmacol. Therap. 17, 1–4.
Concentrations of fenbendazole and of drug metabolites in plasma were measured in buffalo and cross-bred cattle after single intraruminal administration at two different doses. Plasma concentrations of the parent compound fenbendazole and the two metabolites, viz. oxfendazole and fenbendazole sulfone, were much lower in buffalo compared with cattle, at a dose of 7.5 mg/kg body weight as indicated by lower area under concentration curve and concentration maximum. At a dose of 15 mg/kg body weight there were corresponding increases in plasma metabolite concentrations in cattle. However, buffaloes did not show a similar corresponding increase.  相似文献   

19.
Yu, D., Evans, E. R., Hasbrouck, N., Reimschuessel, R., Shaikh, B. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens). J. vet. Pharmacol. Therap.  35 , 560–562. Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us.  相似文献   

20.
采用液质联用方法检测了动物组织(肌肉、肝脏、肾脏、肌肉)中丙硫咪唑亚砜和丙硫咪唑砜含量,采用液液分配的提取方法,用乙酸乙酯、正己烷和甲醇:水(80:20,V/V)对样品进行处理和净化,welchrom-C<,18>(4.6 mm×250 mm,5μm)色谱柱进行液相色谱一质谱法分析.结果显示以S/N=3为检测限,该方法...  相似文献   

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