Uney Kamil, Corum Duygu Durna, Marín Pedro, Coskun Devran, Terzi Ertugrul, Badillo Elena, Corum Orhan
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya 42031, Türkiye.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Hatay Mustafa Kemal, Hatay 31060, Türkiye.
Animals (Basel). 2024 Nov 16;14(22):3302. doi: 10.3390/ani14223302.
Danofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 ± 0.5 °C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t), volume of distribution (V/F), total clearance (CL/F), peak concentration (C), and area under the plasma concentration-time curve (AUC) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 µg/mL, and 82.46 h·µg/mL, respectively. Plasma t, AUC and C increased concomitantly with trout growth, whereas CL/F and V/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. C and AUC were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 µg/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue.
达氟沙星是一种被批准用于鱼类的氟喹诺酮类抗生素。它可用于各种体型鱼类的细菌感染。然而，鱼类因体型不同而存在的生理差异可能会改变达氟沙星的药代动力学，进而影响其治疗效果。在本研究中，首次揭示了不同体型虹鳟鱼体内达氟沙星药代动力学的变化。本研究的目的是比较不同体型虹鳟鱼血浆和组织中的达氟沙星药代动力学。研究在14±0.5℃下对小、中、大体型的鱼进行，以10mg/kg的剂量口服给予达氟沙星。采用高效液相色谱-紫外检测器对组织和血浆中该抗菌药物的浓度进行定量。血浆消除半衰期（t）、分布容积（V/F）、总清除率（CL/F）、峰浓度（C）和血浆浓度-时间曲线下面积（AUC）分别为27.42小时、4.65升/千克、0.12升/小时/千克、2.53微克/毫升和82.46小时·微克/毫升。血浆t、AUC和C随虹鳟鱼生长而增加，而CL/F和V/F则降低。肝脏、肾脏和肌肉组织中的浓度高于血浆。所有组织中，大体型鱼的C和AUC显著高于小体型和中等体型鱼。对于最低抑菌浓度（MIC）阈值分别为0.57、0.79和1.01微克/毫升的细菌，小、中、大体型鱼的标化因子均为1.0。这些结果表明，治疗效果随体型增大而提高。然而，由于大体型鱼组织中达氟沙星浓度的增加可能会影响休药期，因此应注意组织残留风险。
