Aquatic Pathogen Collection Centre of Ministry of Agriculture, Shanghai Ocean University, 999 Hucheng Ring Road, Shanghai, 201306, China.
Shanghai Medicilon & MPI Inc., 585 Chuanda Road, Chuansha Town, Pudong, Shanghai, 201200, China.
Fish Physiol Biochem. 2010 Sep;36(3):677-686. doi: 10.1007/s10695-009-9342-6. Epub 2009 Aug 15.
A drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug which is generally associated with the induction of cytochrome P450s (CYPs) activity. Thus, unexpected treatment failures often happen resulting from inappropriate coadministration in fisheries. However, little information is available about CYP induction in fish. The reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR) belongs to N-demethylation catalyzed mainly by CYP(s). In order to supply useful information on CYP induction, the present study assessed the effects of fish-specific CYP inducers on DIF N-demethylation and enzyme kinetics in kidney cell of Chinese idle (CIK; grass carp (Ctenopharyngodon idellus)) by RP-HPLC. Results demonstrated that the amounts of SAR formation and enzymatic parameters Clint and Vmax were significantly increased due to beta-naphthoflavone (BNF) pretreatment. Therefore, we suggest that CYP1A may be involved in DIF N-demethylation in CIK. This study provides instructive information to ensure treatment success via avoiding CYP induction in fisheries.
当一种药物的效果被另一种药物改变时，就会发生药物-药物相互作用，这种改变通常与细胞色素 P450s（CYPs）活性的诱导有关。因此，在渔业中不合理的联合用药常常导致治疗失败。然而，关于鱼类 CYP 诱导的信息很少。二氟沙星（DIF）生物转化对沙拉沙星（SAR）的反应属于 N-去甲基化，主要由 CYP（s）催化。为了提供关于 CYP 诱导的有用信息，本研究通过反相高效液相色谱法（RP-HPLC）评估了鱼类特异性 CYP 诱导剂对中国鲤（CIK；草鱼（Ctenopharyngodon idellus））肾细胞中 DIF N-去甲基化和酶动力学的影响。结果表明，由于β-萘黄酮（BNF）预处理，SAR 的形成量和酶学参数 Clint 和 Vmax 显著增加。因此，我们认为 CYP1A 可能参与了 CIK 中的 DIF N-去甲基化。本研究为确保通过避免渔业中的 CYP 诱导来获得治疗成功提供了有益的信息。
