Sarafloxacin was orally administered to healthy Yellow River carp ( Cyprinus carpio haematopterus ) maintained at 24 ± 0.5 ℃, at a dose of 20 mg/kg body weight (BW) once daily for six consecutive days. Plasma and tissue samples—including skin + muscle, liver, kidney, gill, intestine, and bile—were collected at 3, 6, and 12 h, and at 1, 3, 5, 7, 10, 12, and 15 days following the last administration. Sarafloxacin concentrations were quantified using high-performance liquid chromatography (HPLC). The drug was widely distributed and detectable in all tissues, with the highest concentration observed in bile (C max = 19.09 μg/mL). A multi-peak phenomenon occurred during the absorption and distribution phases within 0–12 h post-administration and in the late stage of bile distribution. After 12 h, drug concentrations in all tissues except bile gradually declined. By day 10 (240 h), residues persisted in all tissues except plasma and skin + muscle. Non-compartmental analysis (NCA) revealed elimination half-lives (t 1/2λz ) from fast to slow as follows: plasma (45.62 h), liver (60.31 h), skin + muscle (61.58 h), intestine (77.05 h), gill (86.05 h), kidney (88.60 h), and bile (117.46 h). Considering the maximum residue limit (MRL) of 0.03 μg/g in skin + muscle, the withdrawal period was determined as 13 days (or 299 degree-days) based on the upper one-sided 95% confidence interval. In a separate experiment, Yellow River carp were administered the same dosage of sarafloxacin for seven consecutive days. Subsequent Novaseq sequencing revealed that sarafloxacin significantly altered the intestinal microbiota, reducing microbial diversity and reshaping community composition in a time-dependent manner. Following drug withdrawal, the intestinal microbiota gradually returned to baseline levels, similar to the untreated control group. These findings provide essential data for the rational use of sarafloxacin in aquaculture and highlight its potential ecological impacts. • First study of sarafloxacin distribution and residue depletion in Yellow River carp after repeated oral dosing. • Sarafloxacin shows wide distribution, slow elimination, highest in bile; biliary excretion is the main pathway. • Withdrawal period for sarafloxacin in carp skin-on muscle is 13 days (299 ℃-days) based on MRL 0.03 μg/g. • Sarafloxacin alters microbiota, reduces OTU richness, shifts dominant phyla, with partial recovery after withdrawal. • Findings support safe use of sarafloxacin in aquaculture and highlight ecological and food safety implications.
Liu et al. (Thu,) studied this question.