Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations.
The pharmacokinetic (PK) behaviour and clinical efficacy of albendazole (ABZ) against hydatid cysts in mice were assessed after treatment with two different ABZ pharmaceutical formulations. BalbC mice received ABZ (0.5 mg/kg) prepared either as solution or suspension (50 microg/ml) for oral administration (PK study). Blood samples were collected up to 16 h post-treatment and processed to measure ABZ/metabolites concentrations in plasma. The clinical efficacy assessment was performed in BalbC mice infected 8 months earlier with Echinococcus granulosus protoscoleces. Infected animals were allocated into three experimental treatment groups: (a) untreated control, (b) ABZ-solution treated, (c) ABZ-suspension treated. Both treated groups received ABZ (0.5 mg/kg) administered under two different therapeutic schemes: dosing every 48 h over 30 days (regimen I) or treated every 12 h during 15 days (regimen II). Experimental mice were sacrificed 12 h after treatment, and cysts were recovered, weighed and processed for transmission electron microscopy. Enhanced ABZ sulphoxide (the main ABZ metabolite) concentration profiles were measured in animals treated with the ABZ solution. Any positive clinical response was obtained after treatment every 48 h (30 days therapy). However, consistent with the observed PK results, both ABZ formulations were clinically effective in infected mice treated with a 12-h dosing interval (15 days therapy).
Ceballos
Laura
L
Departamento de Fisiopatología, Universidad Nacional del Centro de la Provincia de Buenos Aires, Campus Universitario, 7000, Tandil, Argentina. ceballos@vet.unicen.edu.ar
Elissondo
Celina
C
Moreno
Laura
L
Dopchiz
Marcela
M
Sánchez Bruni
Sergio
S
Denegri
Guillermo
G
Alvarez
Luis
L
Lanusse
Carlos
C
D015766:Albendazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004443:Echinococcosis / Q000188:drug therapy* / Q000469:parasitology; D048209:Echinococcus granulosus / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D019999:Pharmaceutical Solutions; D016896:Treatment Outcome
D000871:Anthelmintics; D019999:Pharmaceutical Solutions; D015766:Albendazole