Pharmacokinetics of marbofloxacin in tilapia (Oreochromis niloticus)
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摘要:目的
研究马波沙星在罗非鱼Oreochromis niloticus体内的药物代谢动力学(简称药动学)特征，为临床合理用药提供参考。
方法将罗非鱼随机分成2组，水温维持在30 ℃，以10 mg·kg-1分别单剂量肌内注射和口服给药，高效液相色谱（HPLC）-荧光检测法测定血浆中马波沙星的质量浓度，用WinNonlin 6.1药动学软件的“非房室模型”分析药动学参数。
结果肌内注射马波沙星后，药物吸收和消除均较口服快，体内分布广泛。达峰时间（tmax）为0.25 h，峰质量浓度（ρmax）为4.31 μg·mL-1，消除半衰期（t1/2λz）为19.21 h，表观分布容积为3.94 L·kg-1，药-时曲线下面积（AUC）为70.36 μg·mL-1·h-1。口服马波沙星后，药物吸收和消除均较慢，体内分布广泛。tmax为4.00 h，ρmax为2.45 μg·mL-1，t1/2λz为22.67 h，表观分布容积为4.27 L·kg-1，AUC为76.66 μg·mL-1·h-1。
结论10 mg·kg-1马波沙星能够有效治疗大多数敏感菌引起的罗非鱼感染。
Abstract:ObjectiveTo study the pharmacokinetics characteristics of marbofloxacin in tilapia(Oreochromis niloticus), and provide references for rational clinical drug usage.
MethodThe tilapia were divided into two groups for intramuscular (i.m.) and oral administrations, and each fish received marbofloxacin at a dosage of 10 mg·kg-1 body mass. Water temperature was maintained at 30 ℃. The concentration of marbofloxacin in plasma was measured using high performance liquid chromatography(HPLC)combined with fluorescence detection. The plasma drug concentration-time data were analyzed by the non-compartment model of WinNonlin 6.1 software.
ResultAfter i.m. administration, marbofloxacin absorption and elimination were relatively faster, and it was widely distributed throughout the body. Peak time of plasma concentration (tmax) was 0.25 h, the maximum plasma concentration (ρmax) was 4.31 μg·mL-1, the elimination half-life (t1/2λz) was 19.21 h, the volume of distribution was 3.94 L·kg-1and the area under the plasma concentration-time curve (AUC) was 70.36 μg·mL-1·h-1. Following oral administration, marbofloxacin absorption and elimination were relatively slower, and it was widely distributed throughout the body. tmax was 4.00 h, ρmax was 2.45 μg·mL-1, t1/2λz was 22.67 h, the volume of distribution was 4.27 L·kg-1 and AUC was 76.66 μg·mL-1·h-1.
ConclusionUsing 10 mg·kg-1 marbofloxacin could effectively control susceptible micro-organisms involved in most common infections in tilapia.
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Keywords:
- marbofloxacin /
- Oreochromis niloticus /
- pharmacokinetics /
- HPLC
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图 1 罗非鱼肌内注射和口服10 mg·kg-1马波沙星后血浆中的药-时曲线
Figure 1. The plasma drug concentration-time curve in tilapia following a single intramuscular or oral administration of 10 mg·kg-1 marbofloxacin
表 1 罗非鱼单剂量肌内注射和口服10 mg·kg-1马波沙星的药代动力学参数1)
Table 1 Pharmacokinetic parameters of marbofloxacin in tilapia following a single intramuscular or oral administration of 10 mg·kg-1 marbofloxacin
给药方式 λz/(h-1) AUC/(μg·mL-1·h-1) tmax/h ρmax/(μg·mL-1) t1/2λz/h 体清除率/(L·h-1·kg-1) 表观分布容积/(L·kg-1) t滞留/h AUMC/(μg·mL-1·h-1) 肌内注射 0.036 70.36 0.25 4.31 19.21 0.14 3.94 21.12 1 485.66 口服 0.031 76.66 4.00 2.45 22.67 0.13 4.27 32.30 2 476.06 1)λz为消除速率常数；AUC为血药浓度-时间曲线下面积；tmax为药物达峰时间；ρmax为药物峰质量浓度；t1/2λz为消除半衰期；t滞留为平均滞留时间；AUMC为一阶矩时间曲线下面积。 
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