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Sulfadiazine의 경구투여에 따른 흰다리새우에서의 약물동태학 및 독성학적 특성 연구

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Alternative Title
Pharmacokinetics and Toxicological characteristic after oral administration of sulfadiazine to whiteleg shrimp, Litopenaeus vannamei
Abstract
This study was conducted to investigate the pharmacokinetic and toxicological properties of sulfadiazine when administered orally to whiteleg shrimp. Feeds containing 80, 240 and 400 mg/kg of sulfadiazine were administered orally at 20℃ and 28℃ for 7 days. After oral administration of sulfadiazine, the amount of drug residue in the tissue (muscle, hemolymph, and hepatopancreas) was analyzed over time using LC-MS/MS. Pharmacokinetic characteristics were derived from the drug residual data using Pk Solver program. Residual amount decreased with time in muscle, hemolymph, and hepatopancreas, and the residual amount increased significantly as the concentration of sulfadiazine increased. In the muscle, hemolymph, and hepatopancreas administered sulfadiazine, the time to reach days of maximum concentration (Tmax) was 0 days at all concentrations, and the maximum concentration (Cmax) was in the order of hemolymph, muscle, and hepatopancreas. In all dose concentration groups, a large amount of sulfadiazine was excreted between 0 and 1 days after the end of the administration, and the residual concentration became less than 0.1 mg/kg on the 3rd day after the end of the administration. The release rate of sulfadiazine was more rapidly at 28 ℃ than at 20 ℃. Biochemical analysis of hemolymph and histopathologic analysis through H&E staining were performed to confirm the toxicity of sulfadiazine to whiteleg shrimp. As a result of biochemical index analysis, the number of hemocytes did not show any significant difference at all concentrations compared to the control group. GOT and total protein were significantly decreased in all concentration groups compared to the control group. GPT, total cholesterol and glucose showed a tendency to decrease in the 80mg/kg concentration group compared to the control group, and rather increase in the high concentration group. As a result of evaluating histopathologic toxicity to muscle, hepatic pancreas, and antennal glands, there was no change in all drug-administered groups compared to the control group. In conclusion, the results of this study on the pharmacokinetic and toxicity evaluation of sulfadiazine can be used as basic data necessary to establish the maximum residue level (MRL) and withdrawal period of sulfadiazine applicable to crustaceans in the future.
Author(s)
이승현
Issued Date
2021
Awarded Date
2021. 2
Type
Dissertation
Keyword
Sulfadiazine 흰다리새우 LC/MS-MS 약물동태학
Publisher
부경대학교
URI
https://repository.pknu.ac.kr:8443/handle/2021.oak/2218
http://pknu.dcollection.net/common/orgView/200000374683
Alternative Author(s)
Seung Hyun Lee
Affiliation
부경대학교 대학원
Department
대학원 수산생명의학과
Advisor
정준기
Table Of Contents
Ⅰ. 서론 1
Ⅱ. 재료 및 방법 3
1. 시약 및 시험동물 3
2. 약제 투여 및 시료 채취 4
3. Sulfadiazine 추출을 위한 시료 전처리 5
3.1. 근육의 전처리 5
3.2. 혈림프의 전처리 6
3.3. 간췌장의 전처리 7
4. LC-MS/MS 분석 조건 8
5. 표준곡선 작성 및 회수율 12
5.1. 근육에서의 회수율 측정 13
5.2. 혈림프에서의 회수율 측정 14
5.3. 간췌장에서의 회수율 측정 15
6. 정확도, 정밀도, 검출한계 및 정량 한계 16
7. 혈액·생화학적 지표 17
7.1. 혈구 계수 17
7.2. T-Cholesterol 17
7.3. Glucose 18
7.4. Total protein 18
7.5. GOT 19
7.6. GPT 19
8. 병리조직학적 독성 20
9. 약물동태학적 분석 21
Ⅲ. 결과 22
1.표준곡선 및 회수율 22
2. 정확도, 정밀도, 검출한계 및 정량한계 24
3. 투여 농도, 온도에 따른 sulfadiazine의 잔류량 변화 25
3.1. 근육에서의 잔류량 변화 25
3.2. 혈림프에서의 잔류량 변화 28
3.3. 간췌장에서의 잔류량 변화 31
4. 약물동태학적 해석 34
4.1. 근육 내 약물동태학적 해석 34
4.2. 혈림프 내 약물동태학적 해석 38
4.3. 간췌장 내 약물동태학적 해석 42
5. 혈액·생화학적 지표 해석 46
6. 병리조직학적 독성 해석 48
Ⅳ. 고찰 52
Ⅴ. 요약 56
Ⅵ. 참고문헌 58
Ⅶ. 감사의 글 64
Degree
Master
Appears in Collections:
대학원 > 수산생명의학과
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