title: 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.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine Department of Medicine I, Medical University of Vienna, Vienna, Austria.|Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Felix
authors.initials: F
authors.lastname: Lötsch
authors.affiliation: Division of Infectious Diseases and Tropical Medicine Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Naderer
authors.affiliation: University Hospital for Infectious Diseases Fran Mihaljevic, Zagreb, Croatia.
authors.forename: Tomislava
authors.initials: T
authors.lastname: Skuhala
authors.affiliation: Division of Infectious Diseases and Tropical Medicine Department of Medicine I, Medical University of Vienna, Vienna, Austria.|Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Groger
authors.affiliation: Department of Medical Parasitology, Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kaczirek
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapie, Medical University of Vienna, Vienna, Austria.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Waneck
authors.affiliation: Division of Infectious Diseases and Tropical Medicine Department of Medicine I, Medical University of Vienna, Vienna, Austria. michael.ramharter@meduniwien.ac.at.|Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon. michael.ramharter@meduniwien.ac.at.|Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany. michael.ramharter@meduniwien.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000378:metabolism* / Q000627:therapeutic use; D003560:Cysts / Q000378:metabolism; D004443:Echinococcosis / Q000188:drug therapy / Q000378:metabolism*; D048209:Echinococcus granulosus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011223:Praziquantel / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D011223:Praziquantel; D015766:Albendazole; C027186:albendazole sulfoxide
keywords: Albendazole; Albendazole-sulphoxide; Cystic echinococcosis; Drug concentration; Echinococcus granulosus; Hydatid disease