歐索林酸在海水魚黃長鰭黃鱲鰺與金目鱸之藥物動力學及殘留試驗

Abstract

台灣是一座海島，地處亞熱帶，屬高溫多濕地區，有利於水產養殖業發展，但近年來水產養殖業常因環境污染及魚蝦貝類感染各種病源菌，而造成大量死亡，使養殖業者遭受巨額的損失。為了減少損失，就會使用各種藥劑來進行消毒殺菌，但也造成藥物殘留的後遺症。 歐索林酸為目前台灣所允許使用的水產藥物之ㄧ，在水產養殖上當作抗生素來使用，在魚病上主要用於運動性產氣單胞菌、愛德華氏菌、弧菌或巴斯德桿菌感染之治療。但因為常檢測到在水產養殖環境中有此抗生素殘留，因而此藥物所造成的殘留與人類公共健康的威脅問題必須有更嚴格的把關。 在進行半衰期試驗單次口服投予60 mg/kg b.w./day歐索林酸後，經由高效液相層析儀分析後的結果顯示，歐索林酸在海水魚長鰭黃鱲鰺血液、肌肉、肝臟及腎臟中的濃度在口服0.5 h後皆達到最高點，其平均濃度為0.43 μg/mL、1.43 μg/g、1.42 μg/g及3.14 μg/g，就結果顯示歐索林酸在於組織中檢測出來的濃度與時間的趨勢，在腎臟濃度為最高，其次為肌肉及肝臟，於血液中濃度最低。歐索林酸在海水魚長鰭黃鱲鰺血液、肌肉、肝臟及腎臟中的半衰期則為50.58 h、25.76 h、45 h及49.15 h；在海水魚金目鱸血液、肌肉、肝臟及腎臟中的濃度在口服1 h後皆達到最高點，其平均濃度為1.55 μg/mL、2.55 μg/g、8.18 μg/g及4.72 μg/g，就結果顯示歐索林酸在於組織中檢測出來的濃度與時間的趨勢，在肝臟濃度為最高，其次為腎臟及肌肉，於血液中濃度最低。歐索林酸在海水魚金目鱸血液、肌肉、肝臟及腎臟中的半衰期則為170.69 h、84.51 h、106.61 h及111.77 h。 在進行殘留試驗五次連續口服投予60 mg/kg b.w./day歐索林酸後，經由高效液相層析儀分析後的結果顯示，歐索林酸在血液在口服投藥結束後的第1天、肌肉在口服投藥結束後的第24天、肝臟在口服投藥結束後的第32天、腎臟在口服投藥結束後的第32天，其平均濃度皆已低於目前動物用藥殘留標準的殘留容許量（0.05 ppm），其停藥期訂為36天；歐索林酸在金目鱸血液在口服投藥結束後的第2天、肌肉在口服投藥結束後的第12天，其平均濃度皆已低於目前動物用藥殘留標準的殘留容許量（0.05 ppm）。但是肝臟在口服投藥結束後的第36天、腎臟在口服投藥結束後的第36天，其平均濃度仍大於目前動物用藥殘留標準的殘留容許量（0.05 ppm），其停藥期訂為18天。

The sea water used for fish culture instead of fresh water in the west-south sea shore of Taiwan was very common. Owing to the land fish pond was not wide, the aquaculture in high density caused the high risks for suffering several diseases. In order to prevent the diseases of fish, not only improving the cultivating environments and techniques, but also tried to use various chemical therapy drugs in clinical use. Taiwan is located in the subtropical area, the water temperature was so often warm that the fish always suffered from viral, bacterial infected diseases, others such as parasite, protozoa, alga and mould were also infestation in fish. An experimental trial was performed to determine the half life of oxolinic acid in sea fish Trachinotus blochii and Lates calcarifer of pharmacokinetic and residue studies. A single dose pharmacokinetic study of oxolinic acid was applied by oral administration at the dose of 60 mg/kg b.w./day. A high performance liquid chromatographic method based on fluorescence detection was developed for determination of oxolinic acid in fish blood, tissue samples. Oxolinic acid in sea fish Trachinotus blochii of peak concentration (Cmax) was obtained directly in the concentration time profile; the residue levels in blood, muscle, liver, and kidney samples after 0.5 h depletion were at the maximum concentration. The Cmax in blood was determined to be 0.43 mg/mL and the half life was calculated to be 50.58 h. The Cmax in muscle was determined to be 1.43 mg/g and the half life was calculated to be 25.76 h. The Cmax in liver was determined to be 1.42 mg/g and the half life was calculated to be 45 h. The Cmax in kidney was determined to be 3.14 mg/g and the half life was calculated to be 25.76 h; Oxolinic acid in sea fish Lates calcarifer of Cmax was obtained directly in the concentration time profile; the residue levels in blood, muscle, liver, and kidney samples after 1 h depletion were at the maximum concentration. The Cmax in blood was determined to be 1.55 mg/mL and the half life was calculated to be 170.69 h. The Cmax in muscle was determined to be 2.55 mg/g and the half life was calculated to be 84.51 h. The Cmax in liver was determined to be 8.18 mg/g and the half life was calculated to be 106.61 h. The Cmax in kidney was determined to be 4.72 mg/g and the half life was calculated to be 111.77 h. An experimental trial was performed to establish an adequate depletion period of oxolinic acid in sea fish Trachinotus blochii and Lates calcarifer of pharmacokinetic and residue studies. The pharmacokinetics of oxolinic acid was applied by oral administration at the dose of 60 mg/kg b.w./day, and was given at a daily dose for five consecutive days. A high performance liquid chromatographic method based on fluorescence detection was developed for determination of oxolinic acid in fish blood, muscle, liver and kidney. Data showed that the average residue levels in sea fish Trachinotus blochii of blood, muscle and kidney decreased to 2.74 ng/mL, 13.82 ng/g, and 21.53 ng/g after 24 days post dosing, respectively; with one exception at 195.01 ng/g in liver tissue. The present study provided data on the depletion of oxolinic acid residues in sea fish Trachinotus blochii after oral administration of five doses of the drug. The residue levels after 24 days depletion decreased to below the maximum residue limits (MRLs) after last oral treatment. At the dosage of 60 mg/kg b.w./day, we suggested that the recommended withdraw period was 36 days; Data also showed that the average residue levels in Lates calcarifer of blood muscle, liver and kidney decreased to MRLs after 2, 12, 36, and 36 days post dosing, respectively. The present study provided data on the depletion of oxolinic acid residues in Lates calcarifer after oral administration of five doses of the drug. The residue levels after 12 days depletion decreased to below the MRLs after last oral treatment. At the dosage of 60 mg/kg b.w./day, we suggested that the recommended withdraw period was 18 days.