Pharmacokinetics and Residue Elimination of Diazepam in Zebrafish

ABSTRACT Diazepam (DZP) residues in aquaculture environments pose a serious threat to food safety. To investigate the pharmacokinetics and residue elimination patterns of DZP using zebrafish as a model organism, a pharmacokinetic study, zebrafish were exposed to 1 mg/L DZP via bath for 24 h. DZP was metabolized to nordiazepam (NDZP), oxazepam (OZP), and temazepam (TZP). Non‐compartmental analysis yielded the following pharmacokinetic parameters: T 1/2 = 4.25–11.78 h; MRT = 3.52–7 h; AUC = 34.51–4222.69 h·μg/kg; Vd = 1.16–6.15 L/kg; CL = 0.14–0.57 L/h/kg. The results indicate that DZP and its metabolites are rapidly absorbed and widely distributed in zebrafish, but eliminated slowly. For the residue elimination study, OZP fell below the LOD (0.05 μg/kg) after 40 days; NDZP and TZP were undetectable after 60 days. DZP persisted at 0.54 ± 0.2 μg/kg on day 150, confirming exceptionally slow elimination. The findings are expected to fill a critical data gap concerning the pharmacokinetics and residue elimination of DZP in zebrafish. These findings provide a framework for extending the results to similar rare edible small fish, thereby aiding in food safety assessment and risk management.