J Med Vet Mycol. 1997 May-Jun;35(3):153-8.
Discrepancy between in vitro and in vivo antifungal activity of albendazole.

Hardin TC, Najvar LK, Rizzo J, Fothergill AW, Rinaldi MG, Graybill JR.

Audie L Murphy Division, South Texas Veterans Health Care System, San Antonio 78284, USA.

Albendazole has in vitro activity against Cryptococcus neoformans and reduced in vitro activity for albendazole when compared with Candida albicans. The major metabolite of albendazole, albendazole sulphoxide showed no in vitro activity against isolates of either fungus. Immunocompetent mice infected intravenously (i.v.) with C. albicans were treated with albendazole doses of 20-600 mg kg-1 per day in noble agar or sesame oil for per oral (PO) administration, or 80 mg kg-1 per day in DMSO for intraperitoneal (i.p.) and i.v. administration for 10 days, and were observed for survival. Mice infected with C. neoformans intracranially received albendazole in daily doses of 600 mg kg-1 prepared in DMSO (i.p.) or peanut butter/rat chow (PO) for 10 days and were observed for survival. Mortality was not different between the treated and control animals in any study. Plasma samples from uninfected mice dosed with similar formulations and doses of albendazole were analysed by HPLC for albendazole and albendazole sulphoxide. No albendazole could be detected in any sample, while concentrations of albendazole sulphoxide (286-8697 ng ml-1) were observed in all samples. These data suggest that the absence of in vivo activity for albendazole is due to rapid conversion to the inactive albendazole sulphoxide metabolite.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9229330&dopt=Abstract albendazole Albenza




Int J Parasitol. 1997 Jul;27(7):781-5.
Albendazole versus ricobendazole (albendazole-sulphoxide) against enteral and parenteral stages of Trichinella spiralis in mice.

Lopez-Garcia ML, Torrado-Duran S, Torrado-Duran J, Martinez-Fernandez AR, Bolas-Fernandez F.

Departamento de Parasitologia, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.

Comparison of the anthelmintic activity and pharmacokinetic profiles following albendazole (ABZ) and albendazole-sulphoxide (ricobendazole = RBZ) administration was made in a mouse model for helminthic infections. Swiss CD-1 mice were experimentally infected with Trichinella spiralis and treated with either ABZ or RBZ at 3 different stages of the parasite life-cycle: pre-adult (day 1 p.i.), migrating larvae (days 13, 14 and 15 p.i.) and encysted muscle larvae (days 34, 35 and 36 p.i.). Plasma concentrations of albendazole-sulphoxide (ABZSO) were measured in age matched non-infected mice by high performance liquid chromatography (HPLC), after administration of ABZ or RBZ dosed at 50 mg ABZ equivalent kg-1. ABZSO pharmacokinetic profiles following ABZ or RBZ administration were similar, although the Tmax (1.83 +/- 0.30 and 0.41 +/- 0.28, respectively) were significantly different (P < 0.01). Against pre-adult stages ABZ was significantly (P < 0.05) more effective than RBZ when administered at 10 mg kg-1 (96.5% and 78.0% reduction with respect to the control group). Migrating and encysted larvae were less sensitive to both compounds and dose rates had to be increased to 100 mg kg-1 to achieve significant efficacies. Against parenteral stages, ABZ was significantly more effective than RBZ when both were given at 100 mg kg-1 (64.0% and 44.2% reduction against migrating larvae and 94.7% and 65.5% reduction against encysted larvae, respectively). In conclusion, RBZ was not more effective than ABZ against enteral and parenteral stages of Trichinella spiralis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9279580&dopt=Abstract albendazole Albenza




Vet Rec. 1997 Aug 2;141(5):120-3.
Prophylactic efficacy of persistent anthelmintics against challenge with drug-resistant and susceptible Ostertagia circumcincta.

Sutherland IA, Leathwick DM, Brown AE, Miller CM.

AgResearch, Grasslands, Palmerston North, New Zealand.

Three groups of newly-weaned Romney lambs were given either a standard oral dose of albendazole, a controlled-release capsule containing albendazole, or a standard oral dose of moxidectin. At 10, 20, 30 and 40 days after treatment, sub-groups of lambs were given 10,000 infective-stage larvae of either a drug-resistant or a drug-susceptible strain of Ostertagia circumcincta. The recommended oral dose of albendazole removed 32 per cent of the resistant strain and over 99.9 per cent of the susceptible O. circumcincta. The recommended oral dose of moxidectin removed 91 per cent of the resistant strain and over 99.9 per cent of the susceptible parasites. None of the lambs treated with controlled-release capsules was challenged at 20 or 30 days after treatment. Twenty-one days after challenge, samples of faeces were taken to determine the presence of nematode eggs and cultured to establish the proportion of eggs developing to infective-stage larvae (L3). Abomasa were recovered after slaughter and worm burdens determined. In the lambs given controlled-release capsules only the resistant parasites were able to establish, and there were significantly fewer than in the lambs treated orally with albendazole. The proportion of the eggs from resistant parasites which developed to L3 was not reduced by the presence of the capsules. Oral moxidectin provided no protection against the establishment of the resistant strain and viable L3 were recovered after challenge with resistant parasites 10 days after treatment; however, the establishment of susceptible O. circumcincta was reduced by more than 99 per cent. The establishment of the susceptible parasites in the lambs treated with moxidectin increased with time and was not significantly l




Vet Rec. 1997 Oct 4;141(14):357-60.
Efficacy of moxidectin, ivermectin and albendazole oral drenches for suppression of periparturient rise in ewe worm egg output and reduction of anthelmintic treatment for lambs.

Taylor SM, Kenny J, Edgar HW, Ellison S, Ferguson L.

Veterinary Sciences Division, Stormont, Belfast.

Sixty multiparous crossbred ewes which had lambed within three days in the first week of April 1996, were divided into four groups. Each group consisted of 15 ewes plus 12 pairs of twins and three single lambs. Group 1 was left untreated, group 2 was treated with albendazole 2.5 per cent drench, group 3 received moxidectin 0.1 per cent drench and group 4 received ivermectin 0.08 per cent drench. The ewes in each group were dosed with their anthelmintic on April 4 (day 0) before being turned out to separate equal-sized paddocks within the same field on the following morning. The field had been used for grazing sheep annually for many years and was considered to be contaminated with infective larvae of the common gastrointestinal nematodes infecting sheep in the region. Faecal samples were collected every two weeks from the ewes and lambs until July 25 (day 112). The lambs in each group were dosed with the anthelmintic used for their dams on day 42, and the dose was repeated when more than 50 per cent of the lambs in any group had a faecal egg count of more than 200 eggs per gram (epg). The total faecal egg output of the treated ewes over days 14 to 70, compared with that of the untreated control group, was reduced by 78.9 per cent by the moxidectin drench, by 47.6 per cent by ivermectin, and by 21.5 per cent by albendazole. The lambs in the groups treated with moxidectin and ivermectin required only one treatment on day 42 before reaching finishing weight; those in the albendazole-treated group were treated twice and the control group once. The faecal egg outputs of the lambs from day 42 until the end of the experiment on day 112 were reduced by 75 per cent by the moxidectin dr




Zhonghua Nei Ke Za Zhi. 1996 Apr;35(4):261-4.
[Continuous therapy with albendazole for hepatic alveolar echinococcosis associated with obstructive jaundice]

[Article in Chinese]

Wang X, Liu Y, Yu D.

Institute of Infectious and Parasitic Diseases, Chongqing University of Medical Sciences, Sichuan.

To observe clinical results of continuous therapy with albendazole for hepatic alveolar echinococcosis associated with obstructive jaundice, we treated 6 patients continuously with albendazole at a dosage of 20 mg.kg-1.d-1. Jaundice disappeared and serum bilirubin level returned to normal within 1-2.5 months in the patients. Ultrasound and/or CT scanning of liver before treatment displayed irregular heterogenous lesions, obscure hilar region with marked intrahepatic biliary dilatation. In one severe jaundiced patient, the common bile duct and the pancreatic duct were dilated and the portal and splenic veins were also distended with marked splenomegaly. Two patients were followed up for 3-9 year after cessation of treatment, their hepatic lesions were almost completely calcified and considered cured. The other four patients were still subjected to treatment one year later. CT and ultrasound scanning showed marked improvement of intrahepatic lesions and disappearance of intrahepatic biliary dilatation. Liver function tests returned to normal except that serum globulin remained elevated in 2 cases. Clinical observation and CT scanning of liver indicated that continuous therapy with albendazole is effective in the treatment of hepatic alveolar echinococcosis associated with obstructive jaundice. No adverse side reactions were seen.

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Antimicrob Agents Chemother. 1997 Dec;41(12):2729-32.
In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives.

Katiyar SK, Edlind TD.

MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA. katiyaruhs.edu

Recent reports have described the successful treatment of Encephalitozoon intestinalis infection in AIDS patients with albendazole. However, this compound is rapidly metabolized in vivo to albendazole sulfoxide, and furthermore it is only 1 of about 15 commercially developed benzimidazole derivatives. To compare the activities of albendazole, albendazole sulfoxide, and other benzimidazoles, an in vitro system involving infection of green monkey kidney cell (E6) monolayers with E. intestinalis spores was developed. After 14 days, the effects of benzimidazoles on spore production were determined. Ten of fourteen derivatives tested, including albendazole, were inhibitory at concentrations of 1 to 10 ng/ml. Derivatives modified at the 1 or 2 position were less active. Albendazole sulfoxide was 1.7-fold more inhibitory than albendazole but significantly less toxic to E6 cells, a finding that explains the clinical efficacy of this compound. Potential alternatives to albendazole are discussed. No albendazole-resistant E. intestinalis mutants were obtained following in vitro selection.

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Int J Parasitol. 1997 Nov;27(11):1333-9.
A new in vitro assay of benzimidazole activity against adult Oesophagostomum dentatum.

Petersen MB, Friis C, Bjorn H.

Department of Pharmacology and Pathobiology, Frederiksberg, Copenhagen, Denmark.

A new in vitro assay of benzimidazole activity against adult Oesophagostomum dentatum is described. The method is based on the ability of O. dentatum to migrate through polyamide nets after exposure to various concentrations of benzimidazole. To determine an appropriate mesh size, control worms and worms exposed to 10 microM oxfendazole for 24 h were allowed to migrate through nets with various mesh sizes (300-500 microns) for up to 1 h. A mesh size of 350 microns and migration periods of 10, 20 and 30 min were selected. Exposure to oxfendazole at 10 microM for 24, 48 and 72 h inhibited the migration in a time-dependent manner. After 72 h of exposure and with a 20-min migration period, the EC50 of oxfendazole for O. dentatum was 0.564 microM. In further studies the activities of albendazole sulphoxide, albendazole, cambendazole, fenbendazole, flubendazole, luxabendazole, mebendazole, oxfendazole, oxibendazole, parbendazole and thiabendazole were compared. The worms were exposed to each drug at two concentrations (0.1 and 3.16 microM) for 72 h. At 3.16 microM there were no significant differences in the activity of the drugs. At 0.1 microM significant differences in activity were found. Albendazole sulphoxide and oxfendazole were poor inhibitors of migration compared with their parent compounds, albendazole and fenbendazole.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9421720&dopt=Abstract albendazole Albenza