Enantiospecific Uptake and Depuration Kinetics of Chiral Metoprolol and Venlafaxine in Marine Medaka ( Oryzias melastigma ): Tissue Distribution and Metabolite Formation.

The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore, the tissue-specific uptake and depuration kinetics of two pairs of pharmaceutical enantiomers, S -(-)-metoprolol versus R -(+)-metoprolol and S -(+)-venlafaxine versus R -(-)-venlafaxine, were studied in marine medaka ( Oryzias melastigma ) during a 28-day exposure and 14-day clearance period. The toxicokinetics of the studied pharmaceuticals, including uptake and depuration rate constants, depuration half-life ( t 1/2 ), and bioconcentration factor (BCF), were reported for the first time. The whole-fish results demonstrated a higher S - than R -venlafaxine bioaccumulation potential, whereas no significant difference was observed between S - and R -metoprolol. O -desmethyl-metoprolol (ODM) and α-hydroxy-metoprolol (AHM) were the main metoprolol metabolites identified by suspect screening, and the ratios of ODM to AHM were 3.08 and 1.35 for S - and R -metoprolol, respectively. N , O -Didesmethyl-venlafaxine (NODDV) and N -desmethyl-venlafaxine (NDV) were the main venlafaxine metabolites, and the ratios of NODDV to NDV were 1.55 and 0.73 for S - and R -venlafaxine, respectively. The highest tissue-specific BCFs of the four enantiomers were all found in the eyes, meriting in-depth investigation.