Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data

Abstract

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)—the first-line anthelminthic drug for medical treatment of CE—is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = −0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (β = −17.2 μg/L/cm; 95th CI, −35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00436-016-5054-x) contains supplementary material, which is available to authorized users.

Combined Albenazole- Praziquantel Treatment in Recurrent Brain Echinococcosis: Case Report

“…In this patient, praziquantel did not increase systemic or CSF availability of ASO, which is in line with the reported high inter-individual variability of the praziquantel-albendazole interaction (13). The intra-cystic ASO concentration appeared low, much lower than reported for non-brain cyst locations (10, 14), but according to the microbiological analysis, it was sufficient to inhibit viability and induce a considerable destruction of protoscolices. Although the observed 3-year remission does not exclude a possibility of a further disease relapse, it is the longest disease-free period in this patient since the initial occurrence of brain hydatidosis in 2009.…”

Hydatid Recurrence Medically Treated by Albendazole

“…The hepatic toxicity of albendazole is well known and can be prevented by temporary discontinuation. On the other hand, long-term medical treatment or perioperative treatment with antiparasitic drugs would be costly for health insurance funds if prescribed to all patients Conventional tools used for monitoring patients with CE include imaging techniques such as ultrasound or CT and serological testing [19,23]. However, serological testing is not of high significance in the evaluation of treatment efficiency as the decrease in antibody titers was delayed by continuous antigen stimulation due to the persistence of parasitic biomass in deal cysts [3].…”

In Vitro and in Vivo Scolicidal Activities of Holothuria leuco-spilota Extract and CeO2 Nanoparticles against Hydatid Cyst

“…Therefore, use of suitable drug therapy, before and after surgery and during aspirations of cysts, can be effective to reduce recurrence, secondary hydatidosis, further surgery and can completely cure the diseases (9). Now according to recommendations of WHO, albendazole and/or mebendazole used in treatment of CE but these synthetic drugs have various side effects, resistance to live, and active pathogens (10, 11).…”