Accumulation and metabolism of drugs and CYP probe substrates in zebrafish larvae

This study examined the accumulation and metabolism of a number of drugs and commonly used probes for human cytochrome P450s (CYPs) in zebrafish larvae under conditions relevant to pharmacological and toxicological assays.Studies with cisapride, chlorpromazine, verapamil, testosterone, and dextromethorphan showed that the zebrafish larvae catalyze a range of phase 1 (oxidation, N-demethylation, O-de-ethylation, and N-dealkylation) and phase 2 (sulfation and glucuronidation) reactions. Both similarities and differences in the metabolic pathways were observed in zebrafish larvae when compared to mammals.Metabolism of phenacetin to paracetamol and dextromethorphan to dextrorphan (metabolic reactions catalyzed by CYP 1A2 and 2D6 in humans respectively) were observed in the zebrafish larvae. In addition the zebrafish larvae 7 days post fertilization (7 d.p.f.) hydroxylated diclofenac, bupropion, tacrine, and testosterone.Although metabolites of several compounds were detected in zebrafish larvae, in the instan...