Reviewing toxicokinetics with a focus on metabolism of new psychoactive substances in the zebrafish (larvae) model

Abstract

Zebrafish (Danio rerio) share around 70% of their genome with humans and many important enzymes for drug metabolism such as some cytochrome p450s have direct orthologs in zebrafish. To date, several studies showed a similar metabolism to humans in general. Furthermore, although using adult fish as model organism requires approval by an Ethics Committee, using larvae until 120 h postfertilization does not necessarily need any approval at least in the European Union. All these aspects seem to be beneficial for using zebrafish (larvae) in toxicokinetic studies for the so-called new psychoactive substances. These compounds are expected to have similar effects as traditional drugs of abuse but are often not listed as controlled drugs when they first appear on the market. However, no information about their toxicokinetics is available when they appear, which is particularly critical concerning their biotransformation. This knowledge is important for example, for developing urine-based screening procedures or for predicting drug–drug interactions. This focus article aims to briefly introduce into the topic of using zebrafish (larvae) in the context of toxicokinetic studies, particularly metabolism studies, and will highlight some aspects such as the route of administration, which are important to consider when using this model. This article is categorized under: Toxicology > New Psychoactive Substances Toxicology > Analytical