Uptake/depuration kinetics, bioaccumulation potential and metabolic transformation of a complex pharmaceutical mixture in zebrafish (Danio rerio).

Uptake and elimination kinetics, bioconcentration factors (BCFs), and metabolic transformation of 20 different pharmaceutically active compounds (PhACs), covering a wide range of therapeutic categories and physico-chemical properties, were studied using zebrafish (Danio rerio). The fish were exposed to the mixture of the selected PhACs at environmentally relevant concentrations similar to 10 µg L−1. The experiments were performed in semi-static conditions and comprised a 7-day uptake period followed by a 7-day depuration period. Most of the PhACs reached a concentration plateau within the 7-day uptake-phase which was followed by an efficient depuration, with the observed uptake (k u) and depuration rate constants (k d,) ranging between 0.002 and 3.752 L kg−1 h−1, and 0.010 to 0.217 h−1, respectively. The investigated PhACs showed low to moderate BCFs. The highest BCFs of 47.8, 28.6 and 47.6 L kg−1 were determined for sertraline, diazepam and desloratadine, respectively. A high contribution of metabolic products to the total internal concentration was observed for some PhACs such as codeine (69%), sulfamethoxazole (51%) and verapamil (87%), which has to be taken into account when assessing the bioconcentration potential. Moreover, most of the metabolites exhibited significantly longer half-lives in zebrafish than their parent compounds and affected the overall depuration kinetics. [Display omitted] • Bioconcentration of a complex pharmaceutical mixture in zebrafish was assessed. • The most bioaccumulative compounds were sertraline, diazepam and desloratadine. • Depuration was very fast, but azithromycin and desloratadine had long half-lives. • Bioconcentration factors of parent drugs were affected by biotransformation. • Most of the metabolites had longer half-lives than their parent compounds. [ABSTRACT FROM AUTHOR]