title: Bioconcentration, metabolism and half-life time of the human therapeutic drug diltiazem in rainbow trout Oncorhynchus mykiss.
abstract: Diltiazem is a human therapeutic drug and a member of the group of calcium channel blockers having widespread use in the treatment of angina pectoris and hypertension. The objective of the present study was to assess the bioconcentration, metabolism, and half-life time of diltiazem in rainbow trout Oncorhynchus mykiss. Juvenile trout were exposed for 21 and 42 days to three nominal concentrations of diltiazem: 0.03 µg L(-1) (environmentally relevant concentration), 3 µg L(-1), and 30 µg L(-1) (sub-lethal concentrations). The bioconcentration factor (BCF) of diltiazem was relatively low (0.5-194) in analysed tissues, following the order kidney > liver > muscle > blood plasma. The half-life of diltiazem in liver, kidney, and muscle was 1.5 h, 6.2 h, and 49 h, respectively. The rate of metabolism for diltiazem in liver, kidney, muscle, and blood plasma was estimated to be 85 ± 9%, 64 ± 14%, 46 ± 6%, and 41 ± 8%, respectively. Eight diltiazem metabolites were detected. The presence of desmethyl diltiazem (M1), desacetyl diltiazem (M2), and desacetyl desmethyl diltiazem (M3) suggests that rainbow trout metabolize diltiazem mainly via desmethylation and desacetylation, similar to mammals. In addition, diltiazem undergoes hydroxylation in fish. At environmentally relevant concentrations, diltiazem and its metabolites were identified in liver and kidney, indicating the potential for uptake and metabolism in non-target organisms in the aquatic environment.
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic. Electronic address: steinbach@frov.jcu.cz.
authors.forename: Christoph
authors.initials: C
authors.lastname: Steinbach
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Grabic
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Ganna
authors.initials: G
authors.lastname: Fedorova
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Koba
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Oksana
authors.initials: O
authors.lastname: Golovko
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Grabicova
authors.affiliation: Research Institute of Fish Culture and Hydrobiology, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Hana Kocour
authors.initials: HK
authors.lastname: Kroupova
mesh_terms: D000818:Animals; D004110:Diltiazem / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014874:Water Pollutants, Chemical; D004110:Diltiazem
keywords: Bioconcentration factor; Calcium channel blocker; Half-life; Metabolites