Dataset Information

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 ?g/L; p?=?0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 ?g/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 ?g/L; p?=?0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (??=?-17.2 ?g/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.

SUBMITTER: Lotsch F

PROVIDER: S-EPMC4958128 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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

Lötsch Felix F Naderer Judith J Skuhala Tomislava T Groger Mirjam M Auer Herbert H Kaczirek Klaus K Waneck Fredrik F Ramharter Michael M

Parasitology research 20160416 8

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, ...[more]

PMID: 27085708

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Project description:BackgroundCystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep.Methodology/principal findingsA randomized placebo-controlled trial was carried out on 118 randomly selected ewes. They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks). Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst. "Noninfective" sheep were those that had no viable PSCs; "low-medium infective" were those that had 1% to 60% PSC viability; and "high infective" were those with more than 60% PSC viability. We evaluated 92 of the 118 sheep. ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%). The percentage of either "noninfective" or "low-medium infective" sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% "noninfective" or "low-medium infective" for placebo. After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal). On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05).Conclusions/significanceWe demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.

Dataset Information

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

Publications

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

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