Effect of cambendazole, thiabendazole, and levamisole on fumarate reductase in cambendazole-resistant and -sensitive strains of Haemonchus contortus.
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Benzimidazoles↗
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Strongyloides ratti and S. stercoralis: the effects of thiabendazole, mebendazole, and cambendazole in infected mice.
The effects of benzimidazole anthelmintics in murine strongyloidiasis were examined. Thiabendazole 50 mg/kg daily produced a 91% reduction in the numbers of Strongyloides ratti larvae in the feces. A similar suppression was seen when thiabendazole was given during the intestinal phase, but no effect was noted when the drug was administered during the phase of larval migration. Thiabendazole had no effect on larvae in the skin or lungs, did not inhibit maturation of worms, and did not expel adult worms from the gut, but did reduce fecundity of adult worms in the intestines by 84%. Mebendazole and cambendazole 50 mg/kg daily totally suppressed excretion of S. ratti in the feces. A similar suppression was seen when the two drugs were given during the phase of larval migration or during the intestinal phase. They had no effect on larvae in the skin, and the reduction in larval numbers in the lungs was not statistically significant. When given during the migratory phase and early intestinal phase, they reduced the numbers of fourth stage larvae recovered from the gut by 95%. Mebendazole and cambendazole totally eliminated intestinal adult worms. Dose response studies indicated that in terms of orally administered dose, cambendazole was 100-1,000 times more active than mebendazole. Thiabendazole and mebendazole had no significant effect on S. stercoralis larvae in the muscles. In contrast, cambendazole 50 mg/kg daily for 4 days eradicated S. stercoralis larvae from the muscles. It is concluded that cambendazole may have significant advantages over both thiabendazole and mebendazole in the treatment of strongyloidiasis.
Animals↗
Critical tests of suspension, paste, and pellet formulations of cambendazole in the horse.
Three formulations of cambendazole were evaluated for anthelmintic activity by critical testing method in 21 horses. Cambendazole suspension was administered via stomach tube at the dose rate of 10 mg/kg to 3 horses and at the dose rate of 20 mg/kg to 3 horses. Cambendazole paste was given intraorally to 8 horses, and the pellet formulation was fed to 7 horses at the dose rate of 20 mg/kg. Anthelmintic activity of cambendazole was similar for all dose rates and formulations. Gasterophilus intestinalis, Gasterophilus nasalis, Draschia megastoma, Anoplocephala perfoliata, and Anoplocephala magna appeared to be refractory. The 3 formulations removed (1) 100% of Parascaris equorum and mature Oxyuris equi, (2) 82 to 100% of Strongylus vulgaris, (3) 80 to 100% of Strongylus edentatus, (4) 85 to 99% of small strongyles, and (5) 79 to 100% of immature Oxyuris equi. Probstmayria vivipara was present in only 1 horse and removal was 99%. There was some evidence of activity on Habronema muscae. Toxicosis was not observed.
Administration, Oral↗
[Effect of albendazole and cambendazole on the egg output of Strongylidae in horses].
The anthelmintic activity of albendazole (5 mg/kg) and cambendazole (20 mg/kg) was compared in twenty-two naturally infected horses and ponies, which were divided into two equal groups. Comparison was based on the faecal strongyle egg counts. On the fourteenth and twenty-eighth days after the first treatment in May, the reductions in faecal egg counts were 99.1 and 93.9 per cent respectively in the albendazole group and 88.0 and 75.7 per cent respectively in the cambendazole group. Within fourty-two days after treatment had been initiated, the mean EPG (eggs per gram) had been restored to the initial level in both groups. The same animals were treated again in August; this time, however, the anthelmintics were changed. In the albendazole group, the faecal egg counts were reduced by more than 95 per cent and, in the cambendazole group, by not more than 84.1 per cent. As the horses were not weighed, the disappointing results obtained with camendazole may have been due to low a dosage, although resistance cannot be ruled out. When the trial was concluded in October, within fifty-six days after treatment in August, the faecal egg counts continued to be remarkably low in both groups: 8.3 per cent of the average EPG prior to treatment in the albendazole group and 21.2 per cent in the cambendazole group. As the trials did not provide any evidence to suggest a larvicidal action of the two anthelmintics, the difference with the results of treatment in May is attributable to an inhibitory effect on the development of the infective Strongyle larvae, specifically Cyathostominae, ingested during the summer.
Albendazole↗
A comparison of the effect of albendazole, cambendazole, and thiabendazole on the larval development of three hymenolepidid cestodes.
Flour beetles (Tribolium confusum) parasitized either by Hymenolepis diminuta, H. nana, or H. microstoma were fed continuously on flour mixed either with thiabendazole, cambendazole, or albendazole (drug concentration was always 10%) from day 1 (24 hr) to day 10 postinfection when the experiments were terminated. All drugs markedly inhibited the development of H. diminuta and H. nana. Populations of these species recovered from beetles fed anthelmintics were composed mostly of under-developed forms, many of which still retained the size and appearance of newly hatched oncospheres, whereas all the parasites recovered from the control beetles (fed only flour) reached full development. Parasites inhibited by cambendazole and albendazole recovered and reached full development within 9 days after treatment was terminated. Also, results were obtained which implied that some parasites were able to continue their development at a reduced rate in the presence of the drugs. Hymenolepis microstoma differed from the other species in its response to the drugs. Albendazole and thiabendazole had no effect on its development and it was only slightly inhibited by cambendazole. Larvae recovered from beetles fed the latter drug had all developed beyond the oncosphere stage but 3 to 5% of them repeatedly failed to reach full development. The drugs varied in their effects on the flour beetles. An average of 63% and 33% of those fed thiabendazole and cambendazole, respectively, died before the 10th day of infection. Albendazole, on the other hand, had no effect on beetle survival.
Albendazole↗
Cambendazole and nondrug macromolecules in tissue residues.
The anthelmintic cambendazole is rapidly metabolized to at least 13 urinary metabolites. Radioactivity was found in liver for weeks after a single dose in cattle, but even at 3 days' withdrawal, cambendazole and metabolites previously identified in urine accounted for only a small fraction of liver radioactivity. The radioactivity was ubiquitously distributed in protein and nucleic acid fractions, and [14C] glutamic acid was identified, indicating incorporation of 14C into the endogenous pool. Part of the residual liver radioactivity at 7 days was convertible chemically to 5-nitrobenzimidazole, indicating a drug-related macromolecular residue. However, data from rats fed radiolabeled steer liver indicate that the residue is minimally bioavailable and therefore of substantially less toxicological concern than cambendazole itself.
Animals↗
Efficacy studies with three formulations of cambendazole in horses.
Treatment with 3 formulations of cambendazole (paste, pellets, and suspension) was compared with thiabendazole treatment in 181 Quarter Horses (females and intact and altered males) of different ages in 2 experiments. The mean output of strongyle eggs, as measured by eggs per gram of feces (epg), was reduced by at least 95% by the 3 formulations of cambendazole compared with pretreatment epg and epg in simultaneously nonmedicated horses. Eggs of Parascaris equorum were seen in 19 of the younger horses in experiment I. Parascaris eggs were not seen in postmedication fecal samples from 14 horses treated wtih cambendazole. Of the 5 horses treated with thiabendazole, 2 had postmedication Parascaris egg counts.
Animals↗
Efficacy of fenbendazole and cambendazole against Muellerius capillaris in dairy goats.
Two anthelmintics, fenbendazole and cambendazole, were used in an attempt to eliminate Muellerius capillaris infections in a group of 44 goats. During the course of this study (508 days), M capillaris larvae were found in at least one fecal specimen from each of 22 of the 44 goats. All 44 goats were dewormed with fenbendazole (30 mg/kg of body weight) at the onset of this study (day 18). Two additional dewormings with fenbendazole at 4- to 8-week intervals were restricted to the goats that continued to shed M capillaris larvae. On the basis of routine fecal examinations, fenbendazole eliminated M capillaris larvae from the feces of 8 (36%) of these 22 goats. On day 253, cambendazole (60 mg/kg) was given orally to 17 of these 22 goats (2 of the 22 had died and 3 were not available for treatment); 13 of these goats were still shedding M capillaris larvae. Cambendazole eliminated M capillaris larvae from the feces of 10 (77%) of these 13 goats chronically infected with M capillaris.
Animals↗
Inheritance of cambendazole resistance in Haemonchus contortus.
Fourth-molt larvae (M4) of cambendazole-resistant (CBZ-R) and cambendazole-susceptible (BPL) strains of Haemonchus contortus were recovered from donor lambs and inoculated orally into source lambs to effect mating in 2nd lamb. Eggs produced by these parasitic matings were collected, cultured, and inoculated into lambs to compare the anthelmintic activity of cambendazole (CBZ), given at a dose rate of 20 mg/kg, against the F1 adults with its activity against the 2 parenteral strains (CBZ-R and PBL). In 2 replications, CBZ was 94% and 99% efficacious against the progeny of the cross matings and 91% and 95% against the BPL strain; CBZ was only 39% and 42% efficacious against the CBZ-R strain. In 1 test of F2 progeny of the reciprocal matings, CBZ was 81.2% efficacious against the F2 adults, whereas CBZ was 97.5% efficacious against the BPL strain and 37% against the CBZ-R strain. The results indicated that heredity of resistance to CBZ in H contortus is not sex-linked and is probably a result of a heterozygous recessive allele. The infective larvae of the CBZ-R groups in these 3 trials were from the 20th and 24th passages through lambs without exposure to any anthelmintics, yet the anthelmintic activity of CBZ ranged from 37% to 42%, indicating that there had been no reversion to susceptibility.
Alleles↗
The effects of thiabendazole, mebendazole and cambendazole in normal and immunosuppressed dogs infected with a human strain of Strongyloides stercoralis.
The effects of three benzimidazole anthelmintics in dogs infected with a human strain of Strongyloides stercoralis were investigated. Cambendazole, but not thiabendazole or mebendazole, abrogated the subsequent development of a patent infection when administered at the same time as infection to immunocompetent dogs. None of the drugs eradicated infection when given after the onset of patency in immunosuppressed animals, although worm burdens were greatly reduced in dogs treated with cambendazole. The implications of these findings for the treatment of patients with strongyloidiasis, particularly those with disseminated infections, are discussed.
Animals↗
Cambendazole in the treatment of human strongyloidiasis.
Cambendazole was used for the treatment of strongyloidiasis in 40 hospitalized patients, given in a single dose of 5 mg/kg body weight. According to the criteria adopted, parasitological cure was obtained in 100% of cases. Side effects were negligible, and did not require interruption of treatment. We therefore conclude that cambendazole is at present the most effective agent for the therapy of human strongyloidiasis.
Adolescent↗
[Effects of Mebendazole and Cambendazole on enterohelminths in pigs].
Mebendazole, administered at a dose of 30 mg active substance per 1 kg of feed, was found to have 100% effectiveness on Ascaris suum and Cambendazole, administered at a dose of 1.5 g per 1 kg of liver weight, showed the same effectiveness in the control of Ascaris suum and Oesophagostomum dentatum. The effectiveness of both drugs on Trichocephalus suis and Strongyloides ransomi was low. Mebendazole and Cambendazole can be recommended for mass dehelminthization of pigs in affected stocks. Helminthoovoscopical examination of sows and fattened pigs showed an 88.6% extensity of invasion in sows, and a 28.3% and 33.9% extensity in three- and five-month-old pigs, respectively. Coccidiosis was found in 51.4% of the sows and Balantidium coli had an occurrence rate of 80.7 to 98.2%.
Animals↗
Effect of cambendazole and haloxon on the carbohydrate metabolism of Ascaridia galli and Heterakis gallinae (Nematoda).
Cambendazole 10(-4) M significantly reduced the level of glycogen in both the parasites. Lactic acid level was found enhanced. Oxygen consumption was suppressed by 63 and 94% in A. galli and H. gallinae, respectively, by 10(-4) M cambendazole. Haloxon did not cause any significant change in glycogen and lactic acid level in either parasite, but reduced oxygen consumption by 23 and 31% in Ascaridia galli and Heterakis gallinae, respectively.
Animals↗
Identification of a glutathione conjugate of cambendazole formed in the presence of liver microsomes.
The incubation of multiply labeled (2H, 3H, 13C, 14C) cambendazole and glutathione with hepatic microsomes from phenobarbital-dosed hamsters results in the formation of polar metabolites. The major metabolite has been characterized by a variety of isotopic, spectrometric, chromatographic, and degradative/synthetic techniques as a glutathione conjugate of cambendazole in which substitution is on the 4-position of the benzimidazole nucleus. The same metabolite is produced by hepatic microsomes from the rat.
Animals↗
Biochemical effects of thiabendazole and cambendazole on Hymenolepis diminuta (Cestoda) in vivo.
An investigation of the chemotherapeutic and biochemical effects of two benzimidazole anthelmintics, thiabendazole (TBZ) and cambendazole (CBZ), on Hymenolepis diminuta in experimentally infected rats is reported. Thiabendazole was active against H. diminuta at a relatively high dosage. A single oral dose of TBZ at 250 mg/kg body weight on day 15 of infection eliminated 100% of the tapeworms as determined at necropsy 5 days after treatment. The chemotherapeutic actions of TBZ on H. diminuta were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TBZ 24 hr earlier were significantly smaller and contained much less glycogen (as a percent of the wet weight) than worms from unmedicated controls. Protein concentrations increased in TBZ-treated worms and at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TBZ-treated worms were significantly lower than the corresponding control values. Cambendazole proved to be five times more potent than TBZ against H. diminuta and produced the same basic changes in worm weight and chemical composition within 18 hr of treatment of the host. Administration of a single oral dose of TBZ or CBZ to the host produced in H. diminuta another change, the onset of which coincided with, or preceded, the gross alterations in worm weight and chemical composition. That change, observed in in vitro studies carried out 14 hr after treatment, revealed that tapeworms from drug-treated rats absorbed and metabolized much smaller quantities of exogenous glucose than did the controls, and the ability of the worm to accumulate glucose against a concentration difference was significantly depressed.
Animals↗
Reproductive function in stallions treated with cambendazole.
Twenty stallions were used to determine if the anthelmintic cambendazole affected seminal characteristics, spermatogenesis, concentration of testosterone in blood serum, or weights of the reproductive orgrans. With minor exceptions, significant differences were not found between values for 10 control and 10 stallions treated with a single oral dose (40 mg/kg body weight) of cambendazole. The treatment did not affect reproductive function and it was concluded that the drug should have no effect on the fertility of stallions.
Animals↗
Control of cambendazole-resistant small strongyles (Population S) with oxibendazole in a pony band: an 8 year field test (1984-1992).
Studies in a band of ponies harboring Population S benzimidazole-resistant small strongyles were initiated in 1974 and have continued for 18 years. Treatment (bimonthly) was with cambendazole for the first 4 years and with oxibendazole (OBZ) for the next 14 years. Data on the first 10 years have been published. The present investigation includes the last 8 years (4 October 1984-11 September 1992), which are the seventh through fourteenth years, of treatment with OBZ. Pre- and posttreatment mean counts of strongyle eggs (epg) and larvae (lpg) per gram of feces were determined biweekly during the current study to monitor the efficacy of OBZ. The average annual percent reductions of epg counts effected by OBZ treatments were 51%, 53%, 38%, 38%, 39%, 28%, 40%, and 19% for the seventh through fourteenth years, respectively. Similar levels of reductions were observed for lpg counts. Although OBZ was initially highly effective on this population of small strongyles, epg and lpg counts gradually declined, but have remained more or less constant since the fifth year of research. However, reductions of the counts were the lowest for the last year of the study.
Animals↗
Comparison of multivariate calibration methods to determine simultaneously mebendazole-cambendazole and mebendazole-thiabendazole in pharmaceutical preparations by UV-visible spectrophotometry.
Three multivariate calibration methods, Principal Component Regression (PCR), the K-matrix method and Q-mode factor analysis followed by varimax and Imbrie's oblique rotations were applied to the simultaneous spectrophotometric determinations of mebendazole (MBZ)-cambendazole (CBZ) and thiabendazole (TBZ)-mebendazole in commercial samples of Exelmin and Helmiben. The calibration set concentrations were selected to contain a +/-10% variation in the quantity of active ingredients as declared by the manufacturer. The Q-mode factor analysis provides superior results for the two pharmaceutical formulations. The K-matrix method proved to be totally inadequate for these determinations. Almost all Q-mode results have relative errors much smaller than 5% of the active ingredient contents. This investigation shows that PCR and Q-mode factor analysis can be used to determine MBZ-CBZ and TBZ-MBZ in commercial drugs.
Calibration↗