Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges

• DOI: 10.1002/dta.2523
• Publication Date: 2018-10-20T12:28:41Z
• Authors: Vinicius Figueire...; Carina de Souza A...; Isabelle Karine d...; Gabriel Reis Alve...; Gustavo Ramalho C...; Aline Reis de Car...; Bruna de Jesus La...; Daniely Silva Oli...; William Dias Ribeiro; Amanda Lessa Dutr...; Monica Costa Padilha; Cleverton Kleiton...; Valeria Pereira d...; Francisco Radler ...; Henrique Marcelo ...
• Keywords: Danio

Abstract Zebrafish ( Danio rerio ) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four compounds. Sibutramine applied the multivariate optimization of ZWT conditions, also comparison among ZWT, humans and mice, beyond role CYP2B6 in ZWT. After optimization, 18 fish 168 hours is minimum requirement a relevant panel biotransformation products. A species resulted observation same hydroxylated metabolites, differences metabolites concentration ratio. However, allowed tuning conditions to obtain specific metabolic profile, depending need. In addition, by utilizing inhibition, pathway demethylation drugs determined. The stereospecificity using selegiline no racemization or inversion transformations were observed. Moreover, investigation cannabimimetics performed JWH‐073 observed are described humans, except hydroxylation at indol group, which explained absence CYP2C9 orthologs zebrafish. Finally, hexarelin used evaluate low stability. As result, displays very fast metabolization all human Therefore, appropriate merits, limitations conduct drug described.