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

Ivanković, Klaudija; Krizman-Matasić, Ivona; Dragojević, Jelena; Mihaljević, Ivan; Smital, Tvrtko; Ahel, Marijan; Terzić, Senka (2024) Uptake/depuration kinetics, bioaccumulation potential and metabolic transformation of a complex pharmaceutical mixture in zebrafish (Danio rerio). Journal of Hazardous Materials, 470 . ISSN 0304-3894

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Abstract

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 (ku) and depuration rate constants (kd,) 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.

Item Type: Article
Uncontrolled Keywords: drugs; fish; metabolites; bioconcentration; biotransformation; PhACs
Subjects: NATURAL SCIENCES > Interdisciplinary Natural Sciences > Environmental Science
Divisions: Division for Marine and Enviromental Research
Projects:
Project titleProject leaderProject codeProject type
Istraživanje farmaceutskog ekspozoma slatkovodnih organizama - procjena rizika i prioritizacija-PHARMA-RISKSenka TerzićIP-2019-04-9519HRZZ
Depositing User: Senka Terzić
Date Deposited: 07 Nov 2024 12:51
URI: http://fulir.irb.hr/id/eprint/9225
DOI: 10.1016/j.jhazmat.2024.134144

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