Plasmodium berghei: The Antimalarial Activity of Albendazole in Rats Is Mediated via Effects on the Hematopoietic System

Dow, G.S.; O’Hara, A.J.; Newton, S.C.; Reynoldson, J.A.; Thompson, R.C.A.

doi:10.1006/expr.2000.4491

Cited by 12 publications

(10 citation statements)

References 13 publications

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“…1,2 In animal studies, specifically in Wistar rats, large doses of albendazole (60-120 mg/ kg/day) have been observed to systematically cause pancytopenia with marked loss of hematopoetic cells in the bone marrow. 10 Albendazole undergoes virtually 100% first-pass metabolism in the liver, and is rapidly converted to albendazole sulfoxide by both the microsomal flavin mono-oxidase and P450 CYP3A enzymes. 11 It then undergoes partial further metabolism to albendazole sulfone via a separate P450-dependent enzyme CYP2C.…”

Section: Discussionmentioning

confidence: 99%

Death Related to Albendazole-Induced Pancytopenia: Case Report and Review

Opatrny¹,

Prichard²,

Snell³

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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Abstract.Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. We report the case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazoleinduced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted.

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Section: Discussionmentioning

confidence: 99%

Death Related to Albendazole-Induced Pancytopenia: Case Report and Review

Opatrny¹,

Prichard²,

Snell³

et al. 2005

The American Journal of Tropical Medicine and Hygiene

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“…To our knowledge, quinine has never been used to treat human microsporidiosis. Interestingly, albendazole, which sometimes acts against microsporidians (see above), is also strongly active against Plasmodium berghei and P. falciparum (Skinner-Adams et al, 1997;Dow et al, 1998Dow et al, , 2000.…”

Section: Comparison Of Therapeutic Efficacy Of Different Antibiotics mentioning

confidence: 99%

New Insect System for Testing Antibiotics

Johny

Lange

Solter

et al. 2007

Journal of Parasitology

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New and efficient methods to screen antibiotics are needed to counter increased antibiotic resistance in pathogens and the emergence of new diseases. Here we report a new insect model for screening antibiotics in vivo using the grasshopper Romalea microptera. The system is inexpensive, efficient, and flexible, avoids animal-welfare problems, and can be used to test against most major pathogenic groups. We employed this system to test 11 commercial antibiotics against a pathogenic Encephalitozoon species (Microsporidia). Oral treatment with fumagillin or thiabendazole significantly reduced pathogen spore counts, whereas spore counts of grasshoppers fed with albendazole, ampicillin, chloramphenicol, griseofulvin, metronidazole, sulfadimethoxine, or tetracycline were not significantly different from the infected controls. Quinine produced a distinct, but nonsignificant, reduction in spores, and streptomycin a nonsignificant increase in spores. Although 2 antibiotics significantly reduced spore counts, in no case was the pathogen totally eliminated. This study demonstrates the validity of this system as a method to screen antibiotics. It also corroborates the difficulty researchers and physicians have had in treating microsporidia infections, and suggests that quinine and related alkaloid compounds should be further examined as possible therapeutic agents against this group of ubiquitous pathogens. In addition, streptomycin and related compounds should be tested to determine if this widely used antibiotic enhances microsporidiosis.

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“…Quant au benzimidazole, du fait de son analogie structurale avec la purine, il constitue le noyau diaza-hétérocyclique de très nombreux médicaments notamment des médicaments anthelminthiques (Jacobs et Taylor, 2001). Par ailleurs, l'on lui attribue des propriétés antiplasmodiales intéressantes depuis les essais de criblage systématique des benzimidazolés anthelminthiques (Mebendazole, Albendazole) (Dow et al, 2000;Canete et al, 2009) (Figure 1), et surtout de celui de l'Astémizole (Figure 1), médicament antihistaminique (Chong et al, 2006). Aussi, nous proposons dans ce travail, la synthèse puis l'évaluation des activités antiplasmodiales de nouveaux hybrides de chalcones obtenus par suite de la juxtaposition du benzimidazole en sa position 2 avec l'enchaînement arylpropénone des chalcones .…”

Section: Introductionunclassified