Mebendazole and related anthelmintics.
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Using the murine sperm-head abnormality test, the mutagenicity of pyrantel pamoate, levamisole, albendazole, mebendazole and niridazole was evaluated. Pyrantel pamoate and niridazole induced increases in sperm-head abnormalities statistically significant over the negative controls at all the dose levels that were considered; the induction was dose-dependent indicating that both drugs might be mutagenic. Levamisole, albendazole, mebendazole and thiabendazole, all were unable to induce statistically significant increases in sperm-head abnormalities over the negative controls at all the dose levels tested; there was no correlation between dose level of administered drugs and incidence of abnormal sperms, indicating that the drugs might not be mutagenic.
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The 'Informal Consultation on the Use of Praziquantel during Pregnancy/Lactation, and Albendazole/Mebendazole in Children under 24 Months' was held 8-9 April 2002, in Geneva, Switzerland.
May 2001 was a landmark in the control of helminth infections. For the first time, the global community recognized that tools existed to deal with some of the commonest infections on the planet. Yet, many of the concepts had been identified nearly a century before, and subsequently largely forgotten. The lessons of the past have much to impart, and recent work has strengthened the evidence and identified the tools to make global control programs feasible. The challenge will now be to make it happen, and some of the problems ahead are truly massive.
The distribution of albendazole (ABZ) and its main metabolites albendazole sulphoxide (ABZSO), albendazole sulphone (ABZSO2) and albendazole 2-aminosulphone (NH2ABZSO2) were investigated in bulk milk and milk products after administration of a single oral dose of the drug (12.5 mg/kg) to 80 Laticauda sheep. An analytical method was developed for this investigation from an existing procedure used for the determination of these compounds in plasma and digesta samples. No traces of the parent compound or NH2ABZSO2 were found in milk or milk products, with the exception of the milk collected 36 h after treatment in which 89 micrograms NH2ABZSO2/kg was detected. Results indicated that ABZ was rapidly oxidized to ABZSO and then to ABZSO2. These metabolites were found at high levels (1-4 mg/kg) in milk collected within 24 h after treatment. Products derived from such milk also contained high concentrations of the two oxidized metabolites, including up to 5 mg ABZSO/kg in Pecorino cheese. Only small quantities of these two metabolites were found in milk collected during the second day after treatment (range 50-500 micrograms/kg). They were no longer detectable in milk collected during the third day after dosing, nor were they found in products made from such milk. These findings confirm that the two polar metabolites ABZSO and ABZSO2 were efficiently excreted from the body. Considering that the established maximum residue limit for ovine milk is 100 micrograms/kg for ABZ plus its metabolites, our results confirmed the appropriateness of the currently prescribed withdrawal time (3 d) after the use of ABZ in lactating sheep. However, considerable levels of ABZSO were detected in milk collected within 24 h after treatment as well as in products and by-products derived from such milk. Owing to the known toxicity of the ABZSO, we stress the need for careful control to ensure adherence to the prescribed withdrawal time.
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Ethyl-6-ethoxybenzothiazole-2-carbamate (Sch 18099) was evaluated for efficacy against natural helminth infections in ponies, pigs, lambs and chickens. Sixteen critical trials were conducted in ponies at dosages of 15 to 150 mg/kg. At 15 mg/kg, efficacy against adult and larval Oxyuris equi was 100% and 91% and against small strongyles it was 98%. Efficacy levels were 95% against Strongylus vulgaris and S. edentatus at the 20 mg/kg dosage. In two trials at 100 mg/kg efficacy against Parascaris equorum was 77%. No efficacy was observed against Gastrophilus spp. or Anoplocephala spp. In swine single oral doses of 10 to 100 mg/kg were not effective. 500 ppm Sch 18099 in the diet for seven days resulted in 100% efficacy against Ascaris suum and Trichuris suis but had no effect on Stongyloides ransomi. Efficacy at 250 ppm against A. suum was 77%. Efficacy at 200 mg/kg in lambs was greater than 90% for Haemonchus contortus, Trichostrongylus axei, Marshallagia marshalli, Bunostomum trignocephalum, Oesophagostomum columbianum, Trichuris ovis, and Chabertia spp. Efficacy was less than 80% for Trichostrongylus vitrinus, Nematodirus filicollis, Ostertagia circumcinta and Cooperia curticei. Except for O. circumcinta and C. curticei, drug efficacy was reduced for these worms in lambs treated at 100 mg/kg. Efficacies of 14.3-89% against Ascaridia galli were obtained with dietary levels of 125-1000 ppm Sch 18099 fed for 7 days. Efficacy of 100% was recorded against Heterakis gallinarum at the 1000 ppm dietary drug level.
F151 was a potent filaricide against adult Brugia pahangi in cats and jirds. HOE 33258 did not kill adult worms in cats but had a marginal effect on adult worms in the peritoneal cavity of jirds. It was not immediately microfilaricidal in cats but the microfilarial counts of treated cats fell within a few weeks of treatment. The reaction product, or mixture, of these two compounds (V5851 = E) was strongly macrofilaricidal in cats and jirds.
Cotugnia digonopora consumes, in 24 hours, glucose equivalent to 38% of its body-weight and converts it into metabolites. The Krebs' cycle is insignificant in the breakdown of glucose because very little CO2 is formed. Ether-extractable acids account for most of the consumed sugar, confirming that metabolism is predominantly anaerobic. Glucose is assimilated as glycogen rather than as nucleic acids, lipids and proteins. Niclosamide, praziquantel and mebendazole strongly inhibit uptake of glucose by the parasite. A considerable increase in the production of lactic acid over that of ether-soluble and volatile acids under the influence of these drugs, suggests a change in the catabolism of sugar towards homolactate fermentation.
Three cows were treated with different levels of compound "E" which is known to have strong filaricidal activity. In all three animals the number of microfilariae of Onchocerca gutturosa declined after treatment. At autopsy most of the adult worms found were dead and in those still living embryogenesis appeared to have ceased. It is concluded that, despite the disadvantages, this system represents a possible way of assessing onchocercicidal activity before undertaking human trials.
This comprehensive review briefly describes the history and pharmacology of albendazole as an anthelminthic drug and presents detailed summaries of the efficacy and safety of albendazole's use as an anthelminthic in humans. Cure rates and 0% egg reduction rates are presented from studies published through March 1998 both for the recommended single dose of 400 mg for hookworm (separately for Necator americanus and Ancylostoma duodenale when possible), Ascaris lumbricoides, Trichuris trichiura, and Enterobius vermicularis and, in separate tables, for doses other than a single dose of 400 mg. Overall cure rates are also presented separately for studies involving only children 2-15 years. Similar tables are also provided for the recommended dose of 400 mg per day for 3 days in Strongyloides stercoralis, Taenia spp. and Hymenolepis nana infections and separately for other dose regimens. The remarkable safety record involving more than several hundred million patient exposures over a 20 year period is also documented, both with data on adverse experiences occurring in clinical trials and with those in the published literature and/or spontaneously reported to the company. The incidence of side effects reported in the published literature is very low, with only gastrointestinal side effects occurring with an overall frequency of just >1% . Albendazole's unique broad-spectrum activity is exemplified in the overall cure rates calculated from studies employing the recommended doses for hookworm (78% in 68 studies: 92%, for A. duodenale in 23 studies and 75% for N. americanus in 30 studies), A. lumbricoides (95% in 64 studies), T. trichiura (48% in 57 studies), E. vermicularis (98% in 27 studies), S. stercoralis (62% in 19 studies), H. nana (68% in 11 studies), and Taenia spp. (85% in 7 studies). The facts that albendazole is safe and easy to administer, both in treatment of individuals and in treatment of whole communities where it has been given by paramedical and nonmedical personnel, have enabled its use to improve general community health, including the improved nutrition and development of children.
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