J Pharm Pharmacol. 1999 Feb;51(2):159-64.
Improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique.

Kohri N, Yamayoshi Y, Xin H, Iseki K, Sato N, Todo S, Miyazaki K.

Department of Pharmacy, Hokkaido College of Pharmacy, Hokkaido University, Sapporo, Japan.

We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when hydroxypropylmethylcellulose and hydroxypropylmethylcellulose phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8 h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10217314&dopt=Abstract albendazole Albenza




Int J Parasitol. 1999 Feb;29(2):305-14.
Influence of ruminal bypass on the pharmacokinetics and efficacy of benzimidazole anthelmintics in sheep.

Steel JW, Hennessy DR.

CSIRO Animal Production, McMaster Laboratory, Blacktown, NSW, Australia. j.steerospect.anprod.csiro.au

Oxfendazole, fenbendazole and albendazole were each administered at 5mgkg(-1) to sheep fitted with abomasal cannulae as a single bolus intra-ruminally or infused intra-abomasally at a declining exponential rate, with half-life equivalent to the rate of rumen fluid outflow. The pharmacokinetic disposition of parent compound and metabolites in plasma and abomasal fluid was determined by high performance liquid chromatography. Compared with intra-ruminal administration, intra-abomasal infusion of fenbendazole lowered the area under the concentration-time curve of drug in both plasma and abomasal fluid; intra-abomasal infusion of albendazole substantially increased maximum drug concentration and the concentration-time curve in abomasal fluid and lowered the plasma concentration time curve of the sulphoxide metabolite; intra-abomasal infusion of oxfendazole increased maximum concentration and the concentration-time curve of drug in plasma and abomasal fluid. The greater availability in abomasal fluid of oxfendazole and albendazole when given at commercial dose rates of 5 mg kg(-1) and 3.9 mg kg(-1), respectively, by intra-abomasal infusion correlated with increased efficacy of both drugs against benzimidazole-resistant Trichostrongylus colubriformis and of albendazole against benzimidazole-resistant Haemonchus contortus over that achieved by intra-ruminal administration as a single bolus.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10221631&dopt=Abstract albendazole Albenza




Antimicrob Agents Chemother. 1999 May;43(5):1052-61.
Efficacies of albendazole sulfoxide and albendazole sulfone against In vitro-cultivated Echinococcus multilocularis metacestodes.

Ingold K, Bigler P, Thormann W, Cavaliero T, Gottstein B, Hemphill A.

Institute of Parasitology, University of Bern, Switzerland.

The metacestode stage of Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a parasitic disease affecting the liver, with occasional metastasis into other organs. Benzimidazole carbamate derivatives such as mebendazole and albendazole are currently used for chemotherapeutic treatment of AE. Albendazole is poorly resorbed and is metabolically converted to its main metabolite albendazole sulfoxide, which is believed to be the active component, and further to albendazole sulfone. Chemotherapy with albendazole has been shown to have a parasitostatic rather than a parasitocidal effect; it is not effective in all cases, and the recurrence rate is rather high once chemotherapy is stopped. Thus, development of new means of chemotherapy of AE is needed. This could include modifications of benzimidazoles and elucidiation of the respective biological pathways. In this study we performed in vitro drug treatment of E. multilocularis metacestodes with albendazole sulfoxide and albendazole sulfone. High-performance liquid chromatography analysis of vesicle fluids showed that the drugs were taken up rapidly by the parasite. Transmission electron microscopic investigation of parasite tissues and nuclear magnetic resonance spectroscopy of vesicle fluids demonstrated that albendazole sulfoxide and albendazole sulfone had similar effects with respect to parasite ultrastructure and changes in metabolites in vesicle fluids. This study shows that the in vitro cultivation model presented here provides an ideal first-round test system for screening of antiparasite drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10223913&dopt=Abstract albendazole Albenza




Vet Parasitol. 1999 Mar 31;82(2):173-8.
Efficacy of closantel plus albendazole liquid suspension against natural infection of gastrointestinal parasites in camels.

Al-Qudah KM, Sharif LA, Al-Rawashdeh OF, Al-Ani FK.

Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid.

Oral administration of closantel in a dose of 10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels naturally infected with various types of gastrointestinal parasites. The camels involved were 15 pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal samples were collected per rectum from all camels at the time of treatment and again 14 and 42 days post treatment. Fecal egg counts and generic determination of third stage larvae was performed. Results indicated that six different species of gastrointestinal tract parasites were identified in camels. Single treatment of closantel plus albendazole mixture reduced egg counts in camels by 100%, 100%, 98% and 77% for Haemonchus longistipes, Ascaris spp., Monezia expansa and Fasciola hepatica, respectively. However, administration of the drug twice on the base of 2 weeks apart significantly raised the efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with various parasites. Camels were not adversely affected by treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10321589&dopt=Abstract albendazole Albenza




N Z Med J. 1999 Apr 23;112(1086):131-4.
Hydatid disease in New Zealand. What remains and how should we treat it?

Lynch AC, Stubbs RS.

Wakefield Gastroenterology Centre, Wakefield Hospital, Wellington.

AIM: The incidence of hydatid disease in New Zealand has steadily declined since the introduction of control measures in the early 1960s. However, patients continue to present for management of newly recognised, disseminated or recurrent disease. It is desirable that doctors in New Zealand have some knowledge of current patterns of presentation and management of the disease. METHODS: Twenty-five patients with hydatid disease have been seen and managed over a ten-year period by one hepato-biliary surgeon. Their presentation and management is outlined and discussed. Surgery, after pre-treatment with albendazole, was undertaken in 15 patients where eradication seemed possible and desirable and in three others presenting with complications (infection, rupture, fistulation). Albendazole treatment alone was used in six patients (five with uncomplicated recurrent or disseminated disease) and one patient has simply been observed. RESULTS: There were no deaths in 18 patients who underwent surgery and no recurrent disease has been found. Major morbidity was confined to those having surgery for complications. All six patients who received albenzadole alone had a good clinical and radiological response, though they required follow-up. CONCLUSIONS: It is suggested that surgery (with albendazole pre-treatment) should be reserved for those with either curable disease or complications and that all others should be managed, in the first instance, by albendazole alone. Providing treatment is instituted before complications develop it should be associated with minimal morbidity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10340690&dopt=Abstract albendazole Albenza




Br J Clin Pharmacol. 2002 Aug;54(2):125-30.
Enantioselective distribution of albendazole metabolites in cerebrospinal fluid of patients with neurocysticercosis.

Takayanagui OM, Bonato PS, Dreossi SA, Lanchote VL.

Faculdade de Medicina de Ribeirao Preto, USP, Ribeirao Preto, Brazil.

AIMS: Albendazole (ABZ) is effective in the treatment of neurocysticercosis. ABZ undergoes extensive metabolism to (+) and (-)-albendazole sulphoxide (ASOX), which are further metabolized to albendazole sulphone (ASON). We have investigated the distribution of (+)-ASOX (-)-ASOX, and ASON in cerebrospinal fluid (CSF) of patients with neurocysticercosis. METHODS: Twelve patients with a diagnosis of active brain parenchymal neurocysticercosis treated with albendazole for 8 days (15 mg kg(-1) day(-1)) were investigated. On day 8, serial blood samples were collected during the dose interval (0-12 h) and one CSF sample was taken from each patient by lumbar puncture at different time points up to 12 h after the last albendazole dose. Albendazole metabolites were determined in CSF and plasma samples by h.p.l.c. using a Chiralpak AD column and fluorescence detection. Population curves for CSF albendazole metabolite concentration vs time were constructed. RESULTS: The mean plasma/CSF ratios were 2.6 (95% CI: 1.9, 3.3) for (+)-ASOX and 2.7 (95% CI: 1.8, 3.7) for (-)-ASOX, with the two-tailed P value of 0.9873 being non-significant. These data indicate that the transport of ASOX through the blood-brain barrier is not enantioselective, but rather depends on passive diffusion. The present results suggest the accumulation of the (+)-ASOX metabolite in the CSF of patients with neurocysticercosis. The CSF AUC(+)/AUC(-) ratio was 3.4 for patients receiving albendazole every 12 h. The elimination half-life of both ASOX enantiomers in CSF was 2.5 h. ASOX was the predominant metabolite in the CSF compared with ASON; the CSF AUC(ASOX)/AUC(ASON) ratio was approximately 20 and the elimination half-life of ASON in CSF was 2.6 h. CONCLUSIONS:




J Vet Pharmacol Ther. 1999 Apr;22(2):77-86.
In vivo and ex vivo uptake of albendazole and its sulphoxide metabolite by cestode parasites: relationship with their kinetic behaviour in sheep.

Alvarez LI, Sanchez SF, Lanusse CE.

Departamento de Fisiopatologia, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Tandil, Argentina.

The current experiments correlate the disposition kinetics of albendazole (ABZ) following its intravenous (i.v.) and intraruminal (i.r.) administrations to Moniezia spp.-infected sheep, with the pattern of drug/metabolite uptake by tapeworms collected from treated animals. The ex vivo uptake pattern of ABZ and albendazole sulphoxide (ABZSO) by the same cestode parasite was also investigated. Naturally infected (Moniezia spp.) Corriedale lambs were treated with ABZ by either i.v. (Group A, n = 15) or i.r. (Group B, n = 15) administration at 7.5 mg/kg. Plasma and abomasal fluid samples were obtained over a 120-h period. Two animals per group were killed at 0.5, 1, 2, 4 and 6 h post-treatment; parasite material (tapeworms), bile and intestinal fluid samples were recovered. Furthermore, Moniezia spp. tapeworms obtained from sheep killed at the local abattoir were incubated with either ABZ or ABZSO for different time periods in a Kreb's Ringer Tris buffer (ex vivo experiments). Samples were analysed by high performance liquid chromatography for ABZ, ABZSO and albendazole sulphone (ABZSO2). ABZ plasma concentrations decreased rapidly and were not detectable beyond 10 h following i.v. administration. ABZSO and ABZSO2 were the metabolites recovered in plasma after both treatments. ABZ and its metabolites were extensively distributed to the digestive tract, mainly into the abomasal fluid, after the i.v. and i.r. administrations. The parent drug and its active ABZSO metabolite were recovered in tapeworms collected from both i.v. and i.r. treated lambs. However, the availability of both ABZ and ABZSO was higher in parasite material recovered from i.v. treated animals