J Dairy Res. 1996 Nov;63(4):533-42.
Distribution of the anthelmintic drug albendazole and its major metabolites in ovine milk and milk products after a single oral dose.

De Liguoro M, Longo F, Brambilla G, Cinquina A, Bocca A, Lucisano A.

Dipartimento di Patologia, Profilassi e di Ispezione degli Alimenti, Napoli, Italia.

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




J AOAC Int. 1996 Nov-Dec;79(6):1281-7.
Rapid quantitative screening assay of trace benzimidazole residues in milk by liquid chromatography.

Fletouris D, Botsoglou N, Psomas I, Mantis A.

Aristotle University of Thessaloniki, School of Veterinary Medicine, Greece.

A simple, rapid, and sensitive liquid chromatographic (LC) assay for quantitative screening of albendazole 2-aminosulfone, albendazole sulfoxide, oxibendazole, oxfendazole, albendazole sulfone, p-hydroxyfenbendazole, albendazole, mebendazole, fenbendazole sulfone, and fenbendazole residues in milk was developed. Samples are made basic (pH 10) and extracted with ethyl acetate. Extracts are partitioned with water, evaporated to dryness, reconstituted with mobile phase, and analyzed isocratically by ion-pair reversed-phase LC at 292 nm. Overall recoveries ranged from 79 to 100%. Linearity was excellent in the fortification range examined (5.3-200 ng/mL). Precision data, based on within- and between-days variations, suggested an overall relative standard deviation of 2.0 to 5.8%. The method was successfully used to quantitate albendazole and fenbendazole and metabolites in milk from 2 drug-treated dairy cows.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8946705&dopt=Abstract albendazole Albenza




Microb Drug Resist. 1996 Fall;2(3):303-8.
Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin.

Upcroft J, Mitchell R, Chen N, Upcroft P.

Queensland Institute of Medical Research, Brisbane, Australia.

Albendazole resistance was induced in three different Giardia cultures following growth in successively increasing amounts of drug. One of the lines was previously resistant to high levels of metronidazole and was able to grow in 2 microM albendazole. The other two survived exposure to 0.8 microM, while normally lethal levels of albendazole against Giardia in vitro were around 0.1-0.2 microM. Albendazole-resistant Giardia were cross-resistant to parbendazole. Major chromosome rearrangements were evident in the line resistant to 2 microM albendazole and IFA with antitubulin antibody indicated differences in the cytoskeleton, particularly the median body, between sensitive and resistant lines. This implicates the cytoskeleton in the mechanism of resistance. Substitution of Tyr for Phe is a consistent beta-tubulin amino acid change in the benzimidazole-resistant helminths and fungi so far analyzed. PCR primers were designed from the published Giardia beta-tubulin gene sequence and spanned the region encoding Phe at position 200. Sequence data from albendazole-resistant Giardia demonstrated that the beta-tubulin gene did not carry a mutation in the codon for amino acid 200. These data suggest that Phe at position 200 in beta-tubulin is not necessary for benzimidazole resistance.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9158790&dopt=Abstract albendazole Albenza




Microb Drug Resist. 1996 Winter;2(4):433-4.
Induction of albendazole resistance in Giardia lamblia.

Lindquist HD.

Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.

Previous studies have shown that Giardia lamblia resistance to metronidazole can be induced in the laboratory, and treatment failures with this drug have also been documented. As replacement therapies, anthelmintic benzimidazoles have antigiardial activity with few clinical side effects. Albendazole has the greatest antigiardial activity of anthelmintic benzimidazoles tested and is effective in vivo. Although Chavez et al. failed to subculture albendazole-exposed G. lamblia, some patient isolates have shown decreased in vitro sensitivity to this drug. In this study, in vitro resistance to albendazole was induced in G. lamblia by a method similar to that reported by Townson et al.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9158815&dopt=Abstract albendazole Albenza




Toxicol Appl Pharmacol. 1997 May;144(1):56-61.
Disposition of netobimin, albendazole, and its metabolites in the pregnant rat: developmental toxicity.

Cristofol C, Navarro M, Franquelo C, Valladares JE, Carretero A, Ruberte J, Arboix M.

Department de Farmacologia i de Terapeutica, Universidad Autonoma de Barcelona, Spain.

Netobimin (NTB), a benzimidazole prodrug with a good anthelmintic spectrum, was administered orally to female rats at a dose of 59.5 mg NTB/kg, to study its pharmacokinetic behavior and the disposition of its most important metabolites, albendazole (ABZ), albendazole sulfoxide (ABZSO), and albendazole sulfone (ABZSO2). ABZ was found in plasma after 6 hr. Peak plasma concentrations (Cmax) and areas under curves (AUC) of ABZSO were eight- and fourfold higher, respectively, than those of ABZSO2. To study NTB disposition in pregnant rats, three different drug doses (50, 59.5, and 70.7 mg/kg) were given. No significant differences were found between plasma concentrations for each metabolite at the three doses studied. Only ABZ concentrations rose slightly as dose increased. ABZ, ABZSO, and ABZSO2 were found in amniotic sacs and embryos at concentrations that were higher than plasma at the same times. The fetuses obtained after administration of each of the doses of NTB were studied to detect developmental toxicity. A significant correlation was found between rate of developmental toxicity and metabolite concentration. ABZSO embryo concentrations could be the main factor accounting for toxicity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9169069&dopt=Abstract albendazole Albenza




Scand J Infect Dis. 1997;29(2):165-7.
Albendazole treatment of human hydatid tissue.

Luchi S, Vincenti A, Messina F, Parenti M, Scasso A, Campatelli A.

Department of Infectious Diseases, Pisa Hospital, Italy.

The effect of albendazole was studied in 12 patients with cystic hydatid disease (CHD) of the liver. Six patients received albendazole continuously for 6 months, while 6 patients received albendazole for 6 courses of 4 weeks with a 2 week drug-free interval between cycles. The continuous therapy proved successful, with stable involution at the follow-up at 24 months, while the patients treated with discontinuous therapy showed improvement or relapse. In our experience, continuous therapy was more effective and can be considered to be a suitable alternative or percutaneous therapy in uncomplicated hydatid liver disease, as an initial treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9181653&dopt=Abstract albendazole Albenza




Antimicrob Agents Chemother. 1997 Jul;41(7):1541-6.
Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro.

Didier ES.

Department of Microbiology, Tulane Regional Primate Research Center, Covington, Louisiana 70433, USA. esdipc.tulane.edu

Presently, the two most commonly used drugs for treating microsporidiosis in persons with AIDS are albendazole and fumagillin. Albendazole is effective for treating disseminated infections due to Encephalitozoon spp. but is variably effective against Enterocytozoon bieneusi infections. Fumagillin is highly effective when used topically to treat ocular infections with Encephalitozoon hellem or Encephalitozoon intestinalis but is too toxic for systemic use. In this study, the fumagillin analog TNP-470 was assayed for antimicrosporidial activity in vitro. The MICs of TNP-470 at which 50% of isolates were killed (MIC50s) were 0.35 +/- 0.21 and 0.38 +/- 0.11 ng/ml for E. intestinalis and Vittaforma corneae, respectively, and were similar to the MIC50s of fumagillin for these organisms, which were 0.515 +/- 0.002 and 0.81 +/- 0.014 ng/ml, respectively. The MIC50 of albendazole for E. intestinalis was 8.0 +/- 4.23 ng/ml, significantly less (P < 0.01) than its MIC50 for V. corneae, which was 55.0 +/- 7.07 ng/ml. TNP-470 inhibited replication of E. intestinalis in RK-13 cells if it was given at the same time as infection or if treatment was initiated 7 days later. In addition, treatment of the infected cultures with TNP-470 at a dose of 10 ng/ml for 2 weeks, followed by discontinuation of the drug treatment, resulted in no significant increase in E. intestinalis shedding during the following 3 weeks in culture. Because TNP-470 acts against both E. intestinalis and V. corneae, and because TNP-470 was found by others to be less toxic in vivo, TNP-470 may be a promising new drug for the treatment of microsporidiosis.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9210681&dopt=Abstract albendazole Albenza