C(9)-奥美拉唑小檗碱衍生物在异育银鲫组织中的分布与药代动力学研究OA

This study investigated the tissue distribution and pharmacokinetic characteristics of a C(9)-berberine derivative substituted with an omeprazole moiety in Carassius auratus gibelio.A single intraperitoneal injection was administered at a dose of 1.5 mg/kg.Bile,liver,intestine,spleen,muscle,kidney,eye,and brain tissues were collected between 3 and 360 hours post-administration.Drug concentrations in these tissues were determined using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF/MS).Key pharmacokinetic parameters were calculated based on non-compartmental analysis(NCA)using PK Solver software.The results revealed significant differences in the distribution and elimination of the derivative across tissues.The highest concentration was observed in bile(Cmax=2161.5±218.7 ng/g),followed by the liver(700.60±42.4 ng/g)and intestine(500.50±25.2 ng/g),while relatively low residual levels were detected in edible tissues such as muscle.Pharmacokinetic parameters indicated prolonged retention in bile,liver,and intestine,with mean residence times(MRT)of 120.92 h,130.62 h,and 67.72 h,respectively;terminal half-lives(T1/2)of 96.43 h,94.38 h,and 52.24 h;and areas under the curve(AUC0-inf)of 112777.30,61711.70,and25706.62 ng·h/g,respectively.The longest T1/2 values were found intheeye(206.43 h)andbrain(201.13 h),with MRT0-infvaluesof341.02 hand329.36 h,suggesting slow elimination from these tissues.In conclusion,the C(9)-omeprazole berberine derivative is rapidly absorbed,widely distributed in metabolic and target organs,and exhibits prolonged retention in Carassius auratus gibelio,supporting its potential as an antibacterial and antiviral agent for aquaculture applications.