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PubMedDate not supplied

Hepatic microsomal metabolism of the anthelmintic benzimidazole fenbendazole: enhanced inhibition of cytochrome P450 reactions by oxidized metabolites of the drug.

Potentiation of the anthelmintic action of benzimidazole carbamates, such as fenbendazole [methyl 5(6)-(phenylthio)-1H-benzimidazol-2-ylcarbamate], has been noted during concurrent administration of benzimidazoles that possess no intrinsic anthelmintic activity. This study investigated the possibility that inhibition of P450 enzymes by fenbendazole and its metabolites could play a role in the potentiation phenomenon. Fenbendazole underwent P450-mediated oxidation in microsomes from untreated rat liver to the sulfoxide and (4'-hydroxyphenyl)thio metabolites [2.92 and 2.87 nmol/(mg of protein.h)]. Pretreatment of rats with phenobarbital or dexamethasone enhanced sulfoxidation by 1.9- and 2.9-fold, respectively. 4'-Hydroxylation was increased slightly (by 28%) by phenobarbital and decreased slightly (by 41%) by dexamethasone. Induction also promoted further metabolism of the sulfoxide to fenbendazole sulfone. Immunoinhibition and chemical inhibition studies suggested that P450 3A proteins and the flavin-containing monooxygenase are involved in sulfoxide and sulfone formation whereas 4'-hydroxylation involved the P450s 2C11, 2C6, and 2B1, depending on the type of induction. In untreated rat liver, the sulfoxide and (4'-hydroxyphenyl)thio metabolites of fenbendazole were relatively potent inhibitors of P450-mediated androstenedione 16 alpha-, 16 beta-, and 6 beta-hydroxylation (IC50 values of 42, 36, and 74 microM, respectively); 7 alpha-hydroxylase activity was uninhibited. In contrast, fenbendazole and its sulfone metabolite were not inhibitors of these reactions. Mixed-function oxidase activities in phenobarbital-induced rat hepatic microsomes were refractory to inhibition by most compounds, but P450 1A1 mediated activities in microsomes from beta-naphthoflavone-induced rat liver were quite susceptible to inhibition by fenbendazole sulfoxide. Studies with two analogous sulfoxides yielded similar findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Anthelmintic activity of extracts of Spondias mombin against gastrointestinal nematodes of sheep: studies in vitro and in vivo.

This study was carried out to validate the efficacy of Spondias mombin, used locally as an anthelmintic, and to standardize the effective dose of the plant extract required for worm control in livestock. In vitro and in vivo studies were conducted to determine the direct anthelmintic effect of ethanolic and aqueous extracts of S. mombin towards different ovine gastrointestinal nematodes. A larval development assay (LDA) was used to investigate the in vitro effect of extracts on strongyle larvae. Another study was conducted in vivo to evaluate the therapeutic efficacy of the extracts administered orally at dose rates of 125, 250, 500 mg/kg to sheep naturally infected with gastrointestinal nematodes. Twenty sheep were selected on the basis of positive faecal egg counts (750 epg). The sheep were allocated randomly to a non-medicated control group (A) or to groups given 125 mg/kg (B), 250 mg/kg (C) or 500 mg/kg (D) of extract, respectively. Sheep in groups B-D were given extracts orally on two days. Individual faecal egg counts were performed on days 0, 3, 6, 9 and 12. The presence of S. mombin extracts in in vitro cultures of larvae decreased the survival of L3 larvae. The LC50 of the aqueous extract of S. mombin was 0.907 mg/ml, while the LC50 of the ethanolic extract was 0.456 mg/ml. This difference in LC50 was statistically significant (p > 0.05). The mean percentage faecal egg reduction of sheep drenched with 500 mg/kg S. mombin extracts was 15.0%, 27.5%, 65.0%, 65.0%, 100.0% against Haenmonchus spp., Trichostrongylus spp., Oesophagostomunm spp., Strongyloides spp. and Trichuris spp. respectively, on day 12. Extracts of S. mombin could find application in the control of helminths in livestock.

Anacardiaceae↗
PubMed2000

Sensitizing capacity of azole derivatives: Part III. Investigations with anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump inhibitors.

BACKGROUND: More than hundred azole derivatives are used today for different purposes. The majority possess antimycotic, antibacterial, anthelmintic, and antiprotozoal properties. They are used as agricultural fungicides; topical antimycotics, and, for example, in antidandruff cosmetics. More recently the antithyroid and antiulcerative activity of certain imimidazoles and benzimidazoles also has been proven, which led to the introduction of proton pump inhibitors and antithyroid drugs to the market. OBJECTIVE: Case reports from the literature and experimental studies suggest that some of the azole derivatives possess a distinct sensitizing potency. Occupational exposure either in the pharmaceutical manufacture or in the pesticide's application by farmers caused allergic contact dermatitis (ACD). However, experimental studies in guinea pigs to determine their sensitizing capacity have been performed only sporadically. METHOD: Guinea pigs were sensitized by a modified Freund's complete adjuvant (FCA) method, with 35 azoles used as agricultural fungicides, proton pump inhibitors, antimycotics, antithyroid agents, antiprotozoals, antimicrobials, anthelmintics, and wood preservatives. RESULTS: Four azoles exhibited a strong sensitizing capacity, 3 a moderate, and 11 a weak sensitizing capacity. Seventeen derivatives remained negative. Among the strong sensitizers were the 3 proton pump inhibitors omeprazole, pantoprazole, and rabeprazole, as well as the antithyroid drug carbimazole. The latter displayed the highest sensitizing power (mean response = 2.50) of all 62 azole derivatives investigated in the present and the 2 previous experimental studies. CONCLUSION: As long as the strong sensitizing azoles are used only systemically the risk of acquiring contact hypersensitivity is low. However, if the idea should arise to use them topically, for example in ointments, tinctures, or lotions against fungal infections, skin problems will probably be observed abundantly.

Animals↗
PubMed2002

Tribulosin and beta-sitosterol-D-glucoside, the anthelmintic principles of Tribulus terrestris.

Successive extracts of Tribulus terrestris prepared using petroleum ether, chloroform, 50% methanol and water were tested for anthelmintic activity in-vitro using the nematode Caenorhabditis elegans. The activity could be detected only in 50% methanol extract which on further bioactivity guided fractionation and chromatographic separation yielded a spirostanol type saponin, tribulosin and beta-sitosterol-D-glucoside. Both the compounds exhibited anthelmintic activity with ED50 of 76.25 and 82.50 microg/ml respectively.

Animals↗
PubMed1982

A survey of nematode control measures used by sheep farmers and of anthelmintic resistance on their farms. Part 2: South Island excluding the Nelson region.

Forty-three randomly selected farms located throughout South Island, excluding the Nelson region, were surveyed for anthelmintic usage and for sheep nematodes resistant to anthelmintics. Most farmers had used both benzimidazole and non-benzimidazole broad-spectrum drenches on their properties in previous years. Sheep were being drenched, on average, 5.6 times within their first year of life but much less frequently thereafter. Commercial interests played the dominant role in helping farmers formulate their drenching policies. On each farm 24 numbered ewe replacement lambs, born during the spring of 1980, were sampled for faeces at the beginning of the trial to provide material for egg counts and larval cultures. The lambs were weighed and divided into three groups of eight. One group received thiabendazole (TBZ) at 66 mg/kg, the second levamisole (LEV) at 8 mg/kg while the third remained untreated as controls. All were resampled 4 to 10 days later. On 32 (88%) of the 40 farms where drenching trials were successfully carried out during autumn 1981, the faecal egg count depression (FECD) following treatment with either drench was 100%. On one farm TBZ was less than 100% effective as gauged by FECD. LEV proved to be less than 100% effective on 7 farms. On one farm the FECD was less than 80%, on 2 between 90% and 95% and on 4 between 95% and 99%.

Journal Article↗
PubMed1986

The persistence of the anthelmintic activity of ivermectin in sheep.

The persistent anthelmintic effect of subcutaneously and orally administered ivermectin given at a dose rate of 0.2 mg/kg was evaluated against experimentally induced infections of Haemonchus contortus, Ostertagia spp., Trichostrongylus spp. and Cooperia curticei in sheep. While both ivermectin treatments apparently resulted in some reduction in the establishment of most of the parasite species examined, only for C. curticei were these reductions statistically significant. For C. curticei, statistically significant antiparasitic activity was evident in animals five and ten days after treatment with ivermectin given by injection and five days after treatment with ivermectin given orally. The possible relevance of these results to parasite control and the potential for selecting for anthelmintic resistance are briefly discussed.

Journal Article↗
PubMed1989

Persistent anthelmintic activity of topically administered ivermectin in cattle.

The persistent anthelmintic effect of ivermectin as a topical treatment at 500 microg/kg was evaluated against induced infections of Ostertagia ostertagi, Trichostrongylus axei and Dictyocaulus vivparus in calves. The results showed a highly significant (P<0.001) anthelmintic activity for at least 14 days against O. ostertagi and T.axei (>99 per cent efficacies) and for at least 28 days (98 per cent efficacy) against D. viviparus.

Journal Article↗
PubMed1990

The detection of anthelmintic resistance by the faecal egg count reduction test: an examination of some of the factors affecting performance and interpretation.

This study examines and compares the possible effects of several procedural variants with those of a currently recommended faecal egg count reduction test for the detection of anthelmintic resistance. The results suggest that the failure of an anthelmintic to reduce the arithmetic mean egg counts of 10-15 animals by at least 90%, from either their pre-treatment levels or from those of an untreated control group 5-10 days later, is likely to be an appropriate procedure. It is recommended that such evaluations of drench performance be regularly conducted on farms. Some suggestions as to how this might be encouraged are made, and the role of larval cultures both in increasing the sensitivity and in enhancing the value of the faecal egg count reduction test are discussed.

Journal Article↗
PubMed1994

Criteria for diagnosing anthelmintic resistance by the faecal egg count reduction test.

This study examines the possible outcome of adopting criteria recommended by the Australian Working Party for defining anthelmintic resistance by the faecal egg count reduction test, namely a mean percentage reduction of less than 95%, together with a lower 95% confidence limit of less than or equal to 90%. Based on an analysis of 313 veterinary diagnostic cases submitted for faecal egg count reduction testing in sheep and goats over a 7-year period, it was found that lower confidence limits of 90% or less were always associated with mean percentage reductions of less than 95%. These results suggest that if anthelmintic resistance is to be defined on the basis of mean faecal egg count reductions of this magnitude, then little practical purpose is likely to be served by further consideration of the lower confidence limits of these estimates.

Journal Article↗
PubMed1997

Persistent anthelmintic activity of topically administered ivermectin in red deer (Cervus elaphus L.) against lungworms (Dictyocaulus viviparus).

A controlled trial was conducted to evaluate the persistent anthelmintic effect of ivermectin as a topical treatment at 500 microg/kg against induced infection with lungworm (Dictyocaulus viviparus) in red deer (Cervus elaphus). The results showed a highly significant (p <0.01) anthelmintic activity for at least 28 days against a newly acquired infection with Dictyocaulus viviparus (>99% efficacy).

Journal Article↗
PubMed1997

Anthelmintic treatment and the suppression of egg production in gastro-intestinal nematodes of sheep and cattle: fact or fallacy?

Evidence for a temporary suppression of egg production in gastro-intestinal nematodes of sheep and cattle following anthelmintic treatment is reviewed and the possible relevance of this phenomenon to the appropriate sampling time in the faecal egg count reduction test is discussed. The results of this review suggest that if such suppressive effects do occur in sheep nematodes, then they are unlikely to be of much practical significance and that little benefit would be derived from extending the post-treatment sampling interval beyond 10 days. For cattle nematodes, however, the issues are less readily obvious but indicate, at least when testing for resistance to persistent anthelmintics, that adoption of a longer post-treatment interval might be advisable.

Journal Article↗
PubMed2001

Consequences of anthelmintic resistance on liveweight gain of lambs on commercial sheep farms.

AIM: To assess the consequences of anthelmintic resistance on commercial sheep farms on liveweight (LW) gains and susceptibility to diarrhoea of growing lambs. METHODS: Five farms with a history of resistance to benzimidazole drenches were selected. On each farm, 150 ewe lambs were randomly allocated to 1 of 3 treatment groups (n=50). Group 1 was treated 5 times at 28-day intervals with oxfendazole (to which nematode resistance had been demonstrated); Group 2 was treated 5 times at 28-day intervals with levamisole or levamisole + oxfendazole (to which nematode resistance had not been demonstrated) and; Group 3 was treated with a combination of slow-release albendazole capsules and oral moxidectin (intended to totally suppress nematode infection). Differentiated faecal egg counts (FECs), FEC reduction tests (FECRT), LW gain and degree of faecal soiling around the breech (dag scores) were determined and compared between groups. RESULTS: Pre-treatment FECs in Group 1 were similar to or slightly lower than those of Group 2. Efficacy of oxfendazole in Group 1 varied between farms and over time within farms, the reduction in FECs after treatment varying from 0% to 95%. The genera identified as resistant on each farm also varied over time. Lambs from Group 3 had lower FECs, lower dag scores and higher growth rates than lambs from Group 2, which in turn had higher LW gains than lambs from Group 1. The overall LW gains during the 5 months of the study were 7.03+/-0.27 kg for Group 1, 8.33+/-0.27 kg for Group 2, and 9.91+/-0.31 kg for Group 3 (mean+/-SEM; means differed significantly from each other, p<0.01). CONCLUSIONS: The decrease in growth rates associated with the continued use of an incompletely effective anthelmintic were surprisingly small in situations where all lambs grazed together.

Journal Article↗
PubMed2002

Production and immunological responses associated with controlled-release-capsule vs 5-drench preventive anthelmintic programmes for parasite control in lambs.

AIMS: To determine whether: a) using a controlled-release anthelmintic capsule (CRC) instead of a programme of 5 oral drenches administered at 3-4 week intervals, would delay the development of anti-parasite immunity in lambs; b) the use of ivermectin instead of albendazole, administered either as a CRC or as a programme of 5 oral drenches, would delay the development of anti-parasite immunity in lambs; c) lambs treated with CRCs would have higher liveweight gains than lambs drenched orally 5 times at 3-4 week intervals, and; d) delayed onset of anti-parasite immunity is associated with reduced liveweight gains in the period following anthelmintic treatment. METHODS: Three field trials were conducted, 1 on a research farm and 2 on commercial sheep farms, in which groups of 30 lambs were treated with either a CRC containing albendazole, a CRC containing ivermectin, 5 oral drenches with albendazole, or 5 oral drenches with ivermectin, administered at 3-4 week intervals. Liveweights and faecal nematode egg counts (FECs) were recorded in all trials. Immunoglobulin-G (IgG) antibody levels to Ostertagia circumcincta and Trichostrongylus colubriformis adult and larval antigens were measured in Trials 1 and 3, and fleece weights and resistance of animals to nematode challenge infection were measured in Trial 1. RESULTS: CRC-treated lambs had higher levels of antibodies to O. circumcincta infective-stage larvae (L3) than orally drenched lambs in Trial 3, but no other immunological differences due to mechanism of delivery were detected. Antibody levels were lower in lambs treated with ivermectin than albendazole, as a CRC or oral drench in Trial 1, but this was not associated with any measurable effects on FEC or productivity. No significant differences (p>0.05) were detected between drench types (albendazole vs ivermectin) or delivery mechanisms (CRC vs oral drenching) in any of the production parameters measured, in any of the trials. Albendazole-CRCs failed to control FECs in all 3 trials. CONCLUSIONS: Although some differences between treatments in antibody levels were detected these were not associated with measurable differences in level of parasitism or productivity of lambs. CRC use did not appear to offer substantial gains in productivity over a structured programme of 5 oral drenches administered at 3-4 week intervals.

Journal Article↗
PubMed1998

Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment.

The provision of vitamin A in food sources of beta-carotene is an alternative to the distribution of high-dose capsules. To examine factors that may influence the success of food-based programs, a study was carried out in Sumatra, Indonesia, of the effect of food sources of beta-carotene, extra dietary fat, and Ascaris lumbricoides infection on serum retinol concentrations in children. Meals and snacks with various amounts of beta-carotene and fat were fed at midday to children 3-6 y of age for 3 wk. Some groups of children were dewormed with the anthelmintic levamisole before the feeding period, whereas others remained infected. Results showed that the incorporation of beta-carotene sources (mainly in the form of red sweet potatoes) into the meal significantly increased serum retinol concentrations. The greatest rise in serum retinol occurred when meals contained added beta-carotene sources and added fat and the children were dewormed. Adding more fat to the meal and deworming the children caused a rise in serum retinol similar to that seen when feeding additional beta-carotene sources. Moreover, the effects of fat and deworming together were additive to the effects of additional beta-carotene sources. When the meal contained additional beta-carotene sources, added fat caused a further improvement in serum retinol concentrations but only if A. lumbricoides infection was low. These studies indicated that food-based interventions in vitamin A-deficient areas might be successful and that other interventions such as increasing dietary fat concentrations and anthelmintic treatment should be considered along with increasing consumption of beta-carotene-rich food.

Animals↗
PubMed1989

Ivermectin as a bird anthelmintic--trials with naturally infected domestic fowl.

To evaluate the use of ivermectin as a bird anthelmintic, 29 White Leghorn hens naturally infected with Ascaridia spp., Heterakis spp. and Capillaria spp. were treated with 0.2, 2 or 6 mg/kg intramuscularly or 0.2 or 0.8 mg/kg orally. Faecal samples were collected before treatment and at autopsy, 2, 6, or 16 days after treatment, when the intestines were also examined for helminths. None of the treatments gave satisfactory anthelmintic results.

Animals↗
PubMed1976

Anthelmintic treatment of young beef cattle in the Wallum region of south-eastern Queensland.

An anthelmintic treatment trial on 125 Brahman-British crossbred 2 to 4 month old calves was undertaken on Wallum country in south eastern Queesland. The calves were divided into 5 experimental groups, grazed together and treated as follows for 17 months: Group 1--Untreated controls; Group 2--Monthly levamisole--niclosamide on 4 occasions; Group 3--Monthly levamisole until 1 month after weaning; Group 4--Levamisole 3 to 6 weeks after saturating rains; Group 5--No levamisole--niclosamide as for Group 2. The mean body weight gains for cattle in Groups 1 to 5 were 95, 124, 105, 121 and 97 kg respectively. Four cattle were lost from each of Groups 1 and 3 and five from Group 5. Most of these losses occurred towards the end of the second summer rainfall season. Faecal egg count maxima were recorded around weaning in untreated groups and during the summer rainfall period of both the first and second summer in all groups. The most prevalent nematode species encountered were H. placei, Cooperia spp and O. ostertagi. It is recommended that in this region cattle under 2 years of age should receive anthelmintic treatment at least in autumn and spring.

Animals↗
PubMed1992

Reduced growth of Lucilia cuprina larvae fed serum from sheep treated with anthelmintics.

The effect of three commonly used anthelmintics, levamisole hydrochloride, ivermectin and closantel, on the development of the sheep blowfly, Lucilia cuprina, was determined. Sheep were treated with each anthelmintic using the manufacturers' recommended dose for helminth control. Both ivermectin and closantel significantly (p < 0.05) reduced the growth rate of larvae of L cuprina cultured in vitro on serum from these sheep. Levamisole hydrochloride had no effect. Ivermectin was effective for less than 6 days after treatment, whereas closantel significantly reduced larval growth 21 days after treatment. Dose-response experiments showed that lower concentrations of both ivermectin and closantel were not as effective in reducing larval growth.

Animals↗
PubMed1984

Prevalence of anthelmintic resistant nematodes in sheep in south-east England.

The prevalence of anthelmintic resistant nematodes among 52 commercial flocks in south-east England was investigated by comparing the faecal egg counts of groups of lambs before, and seven days after, treatment with thiabendazole and levamisole. Evidence of thiabendazole resistance was found on seven farms. in each case Haemonchus contortus was the only species of nematode involved. In vitro egg hatch assays carried out for isolates from these farms gave ED50 estimates of 0.065 to 0.332 micrograms thiabendazole/ml compared with estimates of 0.027 to 0.031 micrograms thiabendazole/ml for a known susceptible strain of H contortus assayed at the same time. In a series of slaughter trials, there was a 17 to 85 per cent reduction, as compared with controls, in the mean worm burdens of groups of lambs infected with these isolates and killed seven days after treatment with thiabendazole, confirming their resistance to this anthelmintic.

Animals↗