Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations.

CEBALLOS, , L.;; ELISSONDO, M.;; L.; MORENO; DOPCHIZ, M; SÁNCHEZ BRUNI, S.;; DENEGRI, G.;; ALVAREZ, L.;; .;LANUSSE, C.

PARASITOLOGY RESEARCH

SPRINGER

Año: 2008 vol. 103 p. 355 - 362

0932-0113

Abstract The pharmacokinetic (PK) behaviour and clinicalThe pharmacokinetic (PK) behaviour and clinical 15 efficacy of albendazole (ABZ) against hydatid cysts in miceefficacy of albendazole (ABZ) against hydatid cysts in mice 16 were assessed after treatment with two different ABZwere assessed after treatment with two different ABZ 17 pharmaceutical formulations. BalbC mice received ABZpharmaceutical formulations. BalbC mice received ABZ 18 (0.5 mg/kg) prepared either as solution or suspension(0.5 mg/kg) prepared either as solution or suspension 19 (50 ìg/ml) for oral administration (PK study). Blood(50 ìg/ml) for oral administration (PK study). Blood 20 samples were collected up to 16 h post-treatment andsamples were collected up to 16 h post-treatment and 21 processed to measure ABZ/metabolites concentrations inprocessed to measure ABZ/metabolites concentrations in 22 plasma. The clinical efficacy assessment was performed inplasma. The clinical efficacy assessment was performed in 23 BalbC mice infected 8 months earlier with EchinococcusBalbC mice infected 8 months earlier with Echinococcus 24 granulosus protoscoleces. Infected animals were allocatedgranulosus protoscoleces. Infected animals were allocated 25 into three experimental treatment groups: (a) untreatedinto three experimental treatment groups: (a) untreated 26 control, (b) ABZ-solution treated, (c) ABZ-suspensioncontrol, (b) ABZ-solution treated, (c) ABZ-suspension 27 treated. Both treated groups received ABZ (0.5 mg/kg)treated. Both treated groups received ABZ (0.5 mg/kg) 28 administered under two different therapeutic schemes:administered under two different therapeutic schemes: 29 dosing every 48 h over 30 days (regimen I) or treatmentdosing every 48 h over 30 days (regimen I) or treatment 30 every 12 h during 15 days (regimen II). Experimental miceevery 12 h during 15 days (regimen II). Experimental mice 31 were sacrificed 12 h after treatment, and cysts werewere sacrificed 12 h after treatment, and cysts were 32 recovered, weighed and processed for transmission electronrecovered, weighed and processed for transmission electron 33 microscopy. Enhanced ABZ sulphoxide (the main ABZmicroscopy. Enhanced ABZ sulphoxide (the main ABZ 34 metabolite) concentration profiles were measured in ani-metabolite) concentration profiles were measured in ani- 35 mals treated with the ABZ solution. Any positive clinicalmals treated with the ABZ solution. Any positive clinical 36 response was obtained after treatment every 48 h (30 daysresponse was obtained after treatment every 48 h (30 days 37 therapy). However, consistent with the observed PK results,therapy). However, consistent with the observed PK results, 38 both ABZ formulations were clinically effective in infectedboth ABZ formulations were clinically effective in infected 39 mice treated with a 12-h dosing interval (15 days therapy).mice treated with a 12-h dosing interval (15 days therapy). 41