两种水温条件下异育银鲫体内双氟沙星药代动力学比较

Pharmacokinetics comparisons of difloxacin in crucian carp(〖WTHX〗Carassais auratus gibebio〖WTHZ〗) at two different water temperatures

摘要:

运用反相高效液相色谱法（RPHPLC），对比了单次口灌20 mg/kg鱼体重剂量条件下，16℃和25℃两种水温时双氟沙星（DIF）在异育银鲫体内代谢动力学差异。数据经过药代动力学软件（3P97）处理，结果显示: 两种温度条件下，双氟沙星药时规律均符合开放性二室模型且存在明显的差异。其中，吸收半衰期（T_1/2Ka）与水温呈正相关，在两种温度条件下分别可达0.010 h和0.122 h；消除半衰期（T_1/2β）、表观分布容积（Vd/F）、血浆和组织中药时曲线下总面积（AUC）等参数则与水温呈负相关，16 ℃条件下血浆T_1/2Ka、Vd/F和AUC分别为70.968 h、1.875/kg和763.761 μg/（mL·h），25 ℃则为18.322 h、0.676/kg和243.244 μg/（mL·h）；16 ℃条件下肝脏组织中AUC为746.622 μg/（mL·h），肾脏组织中AUC为1 095.711 μg/（mL·h），肌肉组织中AUC为1 222.750 μg/（mL·h）；而25 ℃条件下肝脏组织中AUC则为〖KG*5〗294.857 μg/（mL·h），肾脏组织中AUC为258.587 μg/（mL·h），肌肉组织中AUC为344.630 μg/（mL·h）。另外，在两种温度条件下，DIF代谢产物沙拉沙星在血浆及肝脏、肾脏和肌肉组织中均能被检出，且呈多峰现象。结果说明，相对于25 ℃的水温条件，16℃水温时双氟沙星能较好地分布于异育银鲫体内。另外，16 ℃时DIF C_max/MIC₉₀≥10的保持时间可达72 h，而25 ℃时 C_max/MIC₉₀≥10的保持时间仅为4～6 h；因此，双氟沙星在较低水温时（16 ℃）具有更高的药效。

Abstract:

Using reversed phase high performance liquid chromatography(RPHPLC), the pharmacokinetic differences of difloxacin(DIF) with a single dose of 20 mg/kg body weight after oral administration were compared in crucian carp （Carassais auratus gibebio） at the water temperatures of 16 ℃and 25 ℃.Analyzed with Practical Pharmacokinetics Program (3P97)，the results show that the kinetic profiles of DIF，which have significant differences within the two grades temperature, conformed to a twocompartment model, and the absorption halftimes(T_1/2Ka) were 0.009 9 h and 0.122 2 h at 16 ℃and 25 ℃, which were found to have a positive relationship with water temperature, while the elimination halftimes（T_1/2Ka: 70.968 and 18.322 h）,the apparent distribution volumes（Vd/F: 1.875/kg and 0.676/kg）,the area under the concentrationtime curves ［AUC,μg/(mL·h)］ of plasma (763.761 and 243.244) and tissues (746.622，1 095.711，1 222.75and 294.857，258.587，344.63 in liver, kidney and muscle ,respectively) have negative relationships with water temperature. Besides the metabolite of DIF, sarafloxacin (SAR), all can be detected in the plasma and tissues(liver, kidney and muscle) at 16 ℃and 25 ℃, whose kinetic profiles have multimodal phenomenon. The results indicate that the distribution of DIF at 16 ℃ is wider than that at 25 ℃. In addition, the time, when ratio of C_max/MIC₉₀≥10 was greater than or equal to 10 at 16 ℃,could reach 72 h，while it was 4-6 h at 25 ℃;Therefore, DIF may have higher efficacy at low water temperature(16 ℃).