RESUMO
Nicarbazin, a drug used to control the protozoal disease coccidiosis in poultry, is a complex of the highly insoluble drug 4,4'-dinitrocarbanilide with 2-hydroxy-4,6-dimethylpyrimidine. The structures of this and other 4,4'-dinitrocarbanilide complexes have not been determined, but an analogous 2:1 complex of 4,4'-dinitrodiphenylamine with 1,4-diacetylpiperazine has been prepared in which the only possible bonds are hydrogen bonds between the amide carbonyls and amino hydrogens. Scanning electron microscopy revealed that micron-size crystals of nicarbazin disintegrate in water to form much smaller dinitrocarbanilide crystals. Similar complex dissolution in the gut of poultry may account for the greater effectiveness of dinitrocarbanilide when administered as complexed rather than uncomplexed drug. Particle size problems associated with other highly insoluble drugs and pesticides may be resolved by the use of nicarbazin-like complexes.
Assuntos
Carbanilidas/administração & dosagem , Nicarbazina/administração & dosagem , Doenças das Aves Domésticas/prevenção & controle , Animais , Galinhas , Coccidiostáticos , Cristalização , Absorção Intestinal , Solubilidade , Relação Estrutura-AtividadeRESUMO
The effect of MK-401 (4-amino-6-trichloroethenyl 1,3-benzenedisulfonamide) on Fasciola hepatica phosphoglycerate kinase (EC 2.7.2.3) was investigated. MK-401 was a competitive inhibitor of both 3-phosphoglycerate and ATP and had a Ki of 0.29 mM. ATP, 1,3-diphosphoglycerate and MK-401 protected the Fasciola enzyme from inhibition by N-ethylmaleimide. Analogues of MK-401 with different substituents at the 6 position (R = Cl, CF3, C2 F3, C3 F7) were competitive inhibitors of both 3-phosphoglycerate and ATP and a good correlation between the Ki and in vivo activity of these analogues was observed.
Assuntos
Fasciola hepatica/enzimologia , Fosfoglicerato Quinase/antagonistas & inibidores , Sulfanilamidas/farmacologia , Trifosfato de Adenosina/farmacologia , Animais , Ácidos Difosfoglicéricos/farmacologia , Etilmaleimida/farmacologia , Ácidos Glicéricos/farmacologia , Cinética , Relação Estrutura-AtividadeRESUMO
Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation conditions generated from both 1 and 3 the identical aromatic diacetate 11. Good anthelmintic activities in gerbils and sheep for 4"-acetylated derivatives 4 and especially 7 prompted the preparation of additional 4"-acylated derivatives of 2 with pivaloyl, n-octanoyl, succinoyl, carbamoyl, dimethylcarbamoyl and N-acetylglycyl substituents, prepared from the 5-O-tert-butyldimethylsilyl-protected intermediate 12. Other key intermediates were the trichloroethyoxysuccinoyl derivative 18 and 4-nitrophenyl carbonate 21. Anthelmintic activities against Trichostrongylus colubriformis in gerbils comparable in potency to the natural product 2 are shown by the more polar substituted derivatives 20, 23, and 27. Substitution of the 5-hydroxy group or its loss due to aromatization results in drastically reduced anthelmintic potency.
Assuntos
Anti-Helmínticos/síntese química , Ivermectina/análogos & derivados , Lactonas/síntese química , Animais , Fenômenos Químicos , Química , Gerbillinae , Hemoncose/tratamento farmacológico , Lactonas/farmacologia , Ostertagíase/tratamento farmacológico , Ovinos , Tricostrongilose/tratamento farmacológicoRESUMO
The reactions of sulfonate esters of the allylic/homoallylic 13-alcohol of 5-O-(tert-butyldimethylsilyl)-22,23-dihydroavermectin B1a aglycon (1a) were investigated. Nucleophilic substitution gave 13 beta-chloro and 13 beta-iodo derivatives, while solvolytic reaction conditions yielded 13 alpha-methoxy, 13 alpha-fluoro, and 13 alpha-chloro products. A mixture of 13 alpha- and 13 beta-fluorides was obtained upon reaction with DAST. The 13 beta-iodide gave, upon elimination with lutidine, the 8(9),10(11),12(13),14(15)-tetraene. The 13 beta-alcohol and the rearranged 15-ol 13(14)-ene and 15-amino 13(14)-ene derivatives were obtained by substitution via the allylic carbonium ion. MEM ethers 11 and 12 of the two epimeric 13-ols were prepared by alkylation with MEM chloride. In contrast, methylation of 1a with MeI and Ag2O in CH2Cl2 occurred exclusively at the tertiary 7-hydroxy group and not at the secondary 13 alpha-ol. Oxidation of the allylic alcohol 1a proceeded under Swern conditions but not with MnO2 to the 13-oxo aglycon, which was reduced by NaBH4 exclusively to the natural 13 alpha-ol, while reductive amination with NaCNBH3-NH4OAc gave the 13 alpha-amine. The methoxime derivative was obtained in the form of the two geometric isomers. Anthelmintic activities against the sheep nematode Trichostrongylus colubriformis, miticidal activities against the two-spotted spider mite (Tetranychus urticae), and insecticidal activities against the southern armyworm (Spodoptera eridania) as well as the binding constants to a free living nematode (Caenorhabditis elegans) derived receptor assay were obtained and compared to avermectin B1a, 22,23-dihydroavermectin B1a, and the 13-deoxy-22,23-dihydroavermectin B1 aglycon related to the milbemycins. None of the newly prepared derivatives exceeded the potency of the three reference compounds. Lipophilic 13-substituents such as halogen, alkoxy, and methoxime retained high biological activities in all assays, while the more polar substituents hydroxy and amino had weaker activities. Rearranged 15-substituted 13(14)-ene derivatives were completely inactive. The 13-oxo and the 12,13-dehydro analogues were only weakly active in vivo despite having good binding affinity to the receptor, possibly due to instability or poor absorption.
Assuntos
Anti-Helmínticos/síntese química , Ivermectina/análogos & derivados , Animais , Anti-Helmínticos/farmacologia , Ivermectina/síntese química , Ivermectina/farmacologia , Relação Estrutura-AtividadeRESUMO
22,23-Dihydroavermectin B1, ivermectin, derived from avermectin B1 by selective hydrogenation using Wilkinson's homogenous catalyst [Ph3P)3RhCl], was shown to be a highly effective drug for the treatment of a wide variety of metazoan parasitic diseases in animals.
Assuntos
Anti-Helmínticos/síntese química , Lactonas/síntese química , Animais , Anti-Helmínticos/uso terapêutico , Bovinos , Dissacarídeos/síntese química , Dissacarídeos/farmacologia , Helmintíase/tratamento farmacológico , Enteropatias Parasitárias/tratamento farmacológico , Ivermectina , Lactonas/farmacologia , OvinosRESUMO
Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroides dubius in mice. Preliminary screening indicated methyl 6-(1,2,2-trichloroethenyl)imidazo[1,2-alpha]pyridine-2-carbamate to be the most potent derivative in the series. However, evaluation in sheep indicated that its anthelmintic spectrum was inferior to methyl 6-(phenylsulfinyl)imidazo[1,2-alpha]pyridine-2-carbamate.
Assuntos
Anti-Helmínticos/síntese química , Benzimidazóis/síntese química , Imidazóis/síntese química , Animais , Benzimidazóis/farmacologia , Carbamatos/síntese química , Carbamatos/farmacologia , Fenômenos Químicos , Química , Imidazóis/farmacologia , Camundongos , Infecções por Nematoides/tratamento farmacológico , Piridinas/síntese química , Piridinas/farmacologia , Ovinos , Relação Estrutura-AtividadeRESUMO
A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.
Assuntos
Anti-Helmínticos/síntese química , Carbamatos/síntese química , Piridinas/síntese química , Animais , Anti-Helmínticos/uso terapêutico , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Bovinos , Cães , Camundongos , Infecções por Nematoides/tratamento farmacológico , Piridinas/farmacologia , Piridinas/uso terapêutico , Ovinos , SuínosRESUMO
The synthesis and fasciolicidal activity of 4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide are reported. A single dose of 15 mg/kg was effective in removing over 90% of immature Fasciola hepatica from sheep (6 weeks after infection) and calves (8 weeks after infection). A 2.5 mg/kg dose removed over 90% of mature (16 weeks old) liver fluke from sheep. Single oral doses up to 400 mg/kg were tolerated by sheep without gross toxic symptoms.
Assuntos
Anti-Helmínticos/uso terapêutico , Fasciolíase/tratamento farmacológico , Sulfonamidas/uso terapêutico , Animais , Anti-Helmínticos/síntese química , Anti-Helmínticos/toxicidade , Bovinos , Fasciola hepatica , Ovinos , Sulfanilamidas , Sulfonamidas/síntese química , Sulfonamidas/toxicidade , Tricloroetileno/análogos & derivados , Tricloroetileno/síntese química , Tricloroetileno/uso terapêuticoRESUMO
Few studies have examined activity against trematodes for the avermectin/milbemycin class of anthelmintics. To gain insight into this, 12 different members of the avermectin/milbemycin mode of action class were tested against juvenile Fasciola hepatica in a mouse model. The compounds chosen were Avermectin A1, Avermectin A2, Avermectin B1, Avermectin B2, Ivermectin, Ivermectin monosaccharide, Ivermectin aglycone, 13-deoxy ivermectin aglycone, Moxidectin, 13-O-methoxyethoxymethyl ivermectin aglycone, 4"-deoxy-4"-epi-methylamino avermectin B1, and 4"-deoxy-4"-epi-acetylamino avermectin B1 5-oxime. Each of these compounds was administered orally to 4 mice at 2.0 mg kg-1. These mice had been administered 3 metacercariae of F. hepatica 14 days prior to treatment and all mice were necropsied 4 days after treatment. At necropsy, none of the individual avermectin or milbemycin-treated groups showed any significant activity (P > 0.05) against juvenile F. hepatica relative to a vehicle-treated control. In a receptor binding study, adult F. hepatica that had been obtained from sheep were homogenized, their membranes incubated in the presence of 3H-ivermectin, and then measured for high affinity binding sites. The same was done with the free-living nematode, Caenorhabditis elegans. While the C. elegans membranes displayed high affinity 3H-ivermectin binding sites over the range of ivermectin concentrations tested (5-100 nM), no significant 3H-ivermectin binding sites were detected in the F. hepatica membranes. Based on these data, it seems unlikely that any avermectin or milbemycin will show activity against F. hepatica, and certainly makes one pessimistic about possible activity of this mode of action class against trematodes in general.
Assuntos
Antiplatelmínticos/metabolismo , Antiplatelmínticos/uso terapêutico , Fasciola hepatica , Fasciolíase/tratamento farmacológico , Ivermectina/metabolismo , Ivermectina/uso terapêutico , Animais , Antibacterianos , Sítios de Ligação , Caenorhabditis elegans/metabolismo , Membrana Celular/metabolismo , Fasciola hepatica/isolamento & purificação , Fasciola hepatica/fisiologia , Ivermectina/análogos & derivados , Fígado/parasitologia , Macrolídeos/metabolismo , Macrolídeos/uso terapêutico , Camundongos , Relação Estrutura-AtividadeRESUMO
Eprinomectin (MK-397 or 4"-epi-acetylamino-4"-deoxy-avermectin B1) is a novel avermectin selected for development as a topical endectocide for all cattle, including lactating dairy cows. Herein, we show its anthelmintic, insecticidal and miticidal activity. To determine its anthelmintic capabilities, eprinomectin was tested topically on Jersey calves at 0.08, 0.2, or 0.5 mg kg-1 in a probe formulation against experimental infections of adult Haemonchus placei, ostertagia ostertagi, Trichostrongylus axei, T. colubriformis, Cooperia oncophora, C. punctata, Nematodirus helvetianus, Oesophagostomum radiatum and Dictyocaulus viviparus. Eprinomectin removed > or = 99% and > or = 98% of the adult stage of every species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The lowest dosage (0.08 mg kg-1) produced maximal or near maximal efficacy against most of the adult endoparasites with the exception of T. colubriformis (87%) and C. oncophora (88%). In a separate test, eprinomectin was evaluated topically against the immature stages of species at the same dosages. Results showed > or = 99% and > or = 98% removal of the immature stages of each species at the 0.5 and 0.2 mg kg-1 dosage levels, respectively. The 0.08 mg kg-1 dosage maintained > or = 97% efficacy against 6 species with reduced activity against H. placei (42%) and N. helvetianus (66%). For ectoparasites, eprinomectin was tested topically at 0.16, 0.24, 0.32 or 0.5 mg kg-1 on mixed breed cattle naturally infested with the sucking louse, Linognathus vituli. Complete elimination of lice at all dosages was observed by day 14. Topical delivery of eprinomectin at 0.16, 0.24, 0.32 or 0.5 mg kg-1 to Holstein calves experimentally challenged with horn fly, Haematobia irritans, produced 100% efficacy to challenge by week 2 post-treatment in all dosages groups and 94% and 99% efficacy to challenge at the 0.32 and 0.5 mg kg-1 dosage groups, respectively, at week 4. Topical delivery of eprinomectin at 0.16, 0.24 or 0.5 mg kg-1 to Deutsches Fleckvieh cattle infested with mange mites, Chorioptes bovis, produced > or = 95% control at all dosages levels by day 14 post-treatment and was maintained at or near this efficacious level for the 6-week duration of the trial. No adverse reaction was observed in any animal in any of these tests. In summary, these experimental data indicate that eprinomectin is an excellent broad-spectrum endectocide for cattle and is suitable for topical delivery.
Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos , Helmintos/efeitos dos fármacos , Ivermectina/análogos & derivados , Infestações por Ácaros/veterinária , Infecções por Nematoides/veterinária , Doenças dos Ovinos , Administração Tópica , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/toxicidade , Bovinos , Dípteros , Desenho de Fármacos , Feminino , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Ivermectina/toxicidade , Lactação , Infestações por Ácaros/tratamento farmacológico , Ácaros , Infecções por Nematoides/tratamento farmacológico , Ovinos , Relação Estrutura-AtividadeRESUMO
Streptomyces avermitilis normally produces eight avermectins. Avermectin A components contain three methoxyl groups; two on the oleandrose disaccharide and one on the aglycone moiety at C5. Avermectin B components contain methoxyl groups only on the oleandrose disaccharide. Sinefungin inhibits methylation at all three sites. Addition of sinefungin to S. avermitilis Agly-1, a mutant which produces virtually only avermectin aglycone A components, alters the fermentation and causes an accumulation of avermectin aglycone B components. Addition of sinefungin to S. avermitilis 08, a high producing strain, results in accumulation of 8 new avermectins which lack methoxyl groups on the oleandrose moieties as well as the aglycone. These new avermectins were isolated and shown to possess anthelmintic and insecticidal activity.
Assuntos
Anti-Helmínticos/isolamento & purificação , Inseticidas/isolamento & purificação , Ivermectina/análogos & derivados , Lactonas/isolamento & purificação , Streptomyces/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Anti-Helmínticos/farmacologia , Inseticidas/farmacologia , Lactonas/biossíntese , Lactonas/farmacologia , Metiltransferases/análiseRESUMO
A new antiparasitic macrolide, L-155,175, produced by a strain of Streptomyces hygroscopicus, has been isolated; its structure was determined by physico-chemical means. It is active against the tapeworm Hymenolepis diminuta in rats.
Assuntos
Antiprotozoários/isolamento & purificação , Antiprotozoários/análise , Fenômenos Químicos , Química , Meios de Cultura/análise , Fermentação , Espectroscopia de Ressonância Magnética , Microbiologia do Solo , Solventes , Streptomyces/análise , Streptomyces/metabolismo , Relação Estrutura-AtividadeRESUMO
The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3. L-681,110 was isolated from the fermentation broth by acetone extraction of the mycelia, absorption to Amberlite XAD-2 resin and two separations by thin-layer chromatography. The structure of L-681,110 was found to consist of a sixteen-membered lactone with a new type of substitution. The inhibition of ATPase, activity against Caenorhabditis elegans and stimulation of gamma-aminobutyric acid release indicate that L-681,110 possesses some characteristics of both oligomycin and avermectin. L-681,110 was also active against tapeworm and ticks in an in vivo assay.
Assuntos
Lactonas/isolamento & purificação , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Streptomyces/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Caenorhabditis/efeitos dos fármacos , Cestoides/efeitos dos fármacos , Fermentação , Cobaias , Técnicas In Vitro , Lactonas/farmacologia , Masculino , Ratos , Carrapatos/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
A daily oral 5 mg kg-1 dose of clorsulon for 28 days in calves given Fasciola hepatica cysts at 3, 5, and 7 days after initiation of treatment was highly effective in reducing worm burdens (98%) and preventing liver pathology. In similarly infected and treated sheep, clorsulon showed little effect as a prophylactic for delaying the onset of liver pathology. The size of flukes recovered from treated sheep was reduced. Although clorsulon prevented development of fascioliasis in treated calves, the host antibody response was qualitatively similar to that of untreated infected calves, but the magnitude of the response was reduced. Blood clorsulon levels in calves rose to 2.90 micrograms ml-1 within the first week of treatment then fluctuated between 2.65 and 2.90 micrograms ml-1 for the next two weeks. Clorsulon levels in sheep were 0.50-0.60 micrograms ml-1 lower than those in calf blood. The difference in bioavailability of clorsulon between sheep and calves may have contributed to differences in efficacy of the drug.
Assuntos
Antiplatelmínticos/uso terapêutico , Doenças dos Bovinos/prevenção & controle , Fasciolíase/veterinária , Doenças dos Ovinos/prevenção & controle , Sulfanilamidas/uso terapêutico , Administração Oral , Animais , Antiplatelmínticos/administração & dosagem , Antiplatelmínticos/sangue , Disponibilidade Biológica , Bovinos , Fasciola hepatica , Fasciolíase/prevenção & controle , Masculino , Ovinos , Especificidade da Espécie , Sulfanilamidas/administração & dosagem , Sulfanilamidas/sangueRESUMO
The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0.77-15.8 mg/kg) showed that MK-401 was bound predominately to erythrocytes at doses below 4 mg/kg and at higher doses was distributed equally between the red cells and the plasma. Maximum amounts of MK-401 in the blood occurred 2 to 4 hr postadministration and were a hyperbolic function of dose, increasing almost linearly with dose up to 6 mg/kg and then beginning to saturate. Drug uptake by F. hepatica occurred at all doses and increased in direct proportion to the blood level. A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite.
Assuntos
Fasciolíase/tratamento farmacológico , Sulfanilamidas/metabolismo , Fatores Etários , Animais , Relação Dose-Resposta a Droga , Fasciola hepatica , Fasciolíase/metabolismo , Cinética , Masculino , Ratos , Sulfanilamidas/uso terapêuticoRESUMO
A novel laboratory anticestode assay was developed using Hymenolepis diminuta in the hamster. The commercial anticestode compounds, praziquantel, bunamidine, and niclosamide were active against patent infections of Hymenolepis diminuta in golden hamsters (Mesocricetus auratus) when given orally at 3.125, 100, and 200 mg/kg, respectively. The gastrointestinal nematode anthelmintics, cambendazole and mebendazole, were active at 50 mg/kg. Rafoxanide (fasciolicide) was active at 25 mg/kg, the lowest level tested. The coccidiostat, nicarbazin, was active at experimental levels (800 mg/kg and up). The anthelmintic-ectoparasiticide (endectocide), ivermectin, was inactive against the tapeworm at 0.5 mg/kg, as expected.
Assuntos
Anticestoides/uso terapêutico , Sistema Digestório/parasitologia , Himenolepíase/tratamento farmacológico , Hymenolepis/efeitos dos fármacos , Administração Oral , Amidinas/administração & dosagem , Amidinas/farmacologia , Amidinas/uso terapêutico , Animais , Anticestoides/administração & dosagem , Anticestoides/farmacologia , Cambendazol/administração & dosagem , Cambendazol/farmacologia , Cambendazol/uso terapêutico , Cricetinae , Modelos Animais de Doenças , Hymenolepis/isolamento & purificação , Insetos Vetores/parasitologia , Intestino Delgado/parasitologia , Ivermectina/administração & dosagem , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Masculino , Mebendazol/administração & dosagem , Mebendazol/farmacologia , Mebendazol/uso terapêutico , Mesocricetus , Nicarbazina/administração & dosagem , Nicarbazina/farmacologia , Nicarbazina/uso terapêutico , Niclosamida/administração & dosagem , Niclosamida/farmacologia , Niclosamida/uso terapêutico , Praziquantel/administração & dosagem , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Rafoxanida/administração & dosagem , Rafoxanida/farmacologia , Rafoxanida/uso terapêutico , Distribuição Aleatória , Tribolium/parasitologiaRESUMO
The ability of an in vivo anticoccidial assay to identify potential feed-through insecticides was demonstrated using first-instar Lucilia sericata on droppings from chicks fed medicated diets. Cyromazine, a commercially available feed-through insect growth regulator, ivermectin, diflubenzuron, fipronil, permethrin, and 2 experimental compounds were effective in varying degrees in killing L. sericata larvae. Eleven coccidiostats were effective against the protozoan parasites (Eimeria spp.) at commercially used levels, whereas they were ineffective against Lucilia larvae.
Assuntos
Coccidiostáticos/farmacologia , Dípteros/efeitos dos fármacos , Eimeria/efeitos dos fármacos , Fezes/química , Inseticidas/análise , Ração Animal , Animais , Galinhas , Inseticidas/farmacologia , Permetrina/análise , Permetrina/farmacologia , Triazinas/análise , Triazinas/farmacologiaRESUMO
Paraherquamide was 98 to 100 per cent effective against six-day-old Trichostrongylus colubriformis infections in gerbils when given as single oral doses of 1.56 mg kg-1 and above. Doses of 0.78 or 0.39 mg kg-1 were 96 and 66 per cent effective, respectively. A single oral dose of 200 mg kg-1 was well tolerated.
Assuntos
Anti-Helmínticos/uso terapêutico , Indolizinas/uso terapêutico , Compostos de Espiro/uso terapêutico , Tricostrongiloidíase/tratamento farmacológico , Tricostrongilose/tratamento farmacológico , Administração Oral , Animais , Anti-Helmínticos/administração & dosagem , Feminino , Gerbillinae , Indolizinas/administração & dosagem , Masculino , Estrutura Molecular , Compostos de Espiro/administração & dosagemRESUMO
This report describes a novel assay for the detection of gastrointestinal anthelmintics using mice infected with Haemonchus contortus and adapted to the 1 animal/test group protocol. Mice infected with both H. contortus and Heligmosomoides polygyrus were fed ivermectin-medicated diets for 6 days. A dietary level of 0.09375 ppm was 98.1% effective against the 0- to 6-day-old abomasal stomach worm of sheep, whereas a level of 0.75 ppm reduced the 3- to 9-day-old H. polygyrus worm burden by 94.0%. H. contortus was approximately 8-fold more sensitive to ivermectin than was H. polygyrus in this model. The sensitivity of this assay rivals that of the gerbil-Trichostrongylus colubriformis model while utilizing a more economical host.