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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.9
- 수록면
- 277 - 286 (10page)
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The minipig is becoming increasingly used as a test animal both in pharmacological and toxicological studies of new drugs. Coumarin is a natural product which presents in foodstuffs and use in clinical medicine. However, coumarin shows marked toxicity in some species of animals and species differences in toxicity depend on metabolic activation of coumarin. Enzymatic process of coumarin metabolism in minipig is similar to that of human. This study was conducted to compare the toxicity data of coumarin in the minipig with other animal species and to confirm the usefulness of minipig in the regulatory toxicity studies. Single and 28 day repeated-dose toxicity studies of coumarin were conducted using minipigs. In the single dose toxicity study, maximum tolerated dose (MTD) value of coumarin was determined to be a 200 ㎎/㎏/day and liver was decided as a target organ. Based on the single dose toxicity study, twenty-eight day repeated dose study was conducted at dose levels of 0, 50, 100, and 200 ㎎/㎏/day. Middle and high dose minipigs showed clinical signs and pathological lesions in the liver and kidneys. Low dose group minipigs did not display any clinical signs and functional abnormalities considered to have relation with coumarin treatment, but showed significant increase of liver weight. From the above findings, no observable effect level (NOEL) of minipig was determined to be below 50 ㎎/㎏/day.
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재료 및 방법
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감사의 글
참고문헌
참고문헌 (24)
참고문헌 신청
Anzenbacher, P. , 1998 , Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples , Drug Metab. Disp 26 : 56 ~ 59
Balls, M. , 1994 , Replacement of animal procedures: alternatives in research, education and testing , Lab. Anim 28 : 193 ~ 211
Boggards, J.J.P. , 2000 , Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man , Xenobiotica 30 : 1131 ~ 1152
Bollen, P. , 1997 , The gottingen minipig in pharmacology and toxicology , Pharmacol. Toxicol 80 (suppl. 2) : 3 ~ 4
Clausing, P. , 1986 , On the usefulness of minipigs in toxicology testing of pesticides , Arch. Toxicol 9 (suppl. 1) : 225271 ~
Balls, M. , 1994 , Replacement of animal procedures: alternatives in research, education and testing , Lab. Anim 28 : 193 ~ 211
Boggards, J.J.P. , 2000 , Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man , Xenobiotica 30 : 1131 ~ 1152
Bollen, P. , 1997 , The gottingen minipig in pharmacology and toxicology , Pharmacol. Toxicol 80 (suppl. 2) : 3 ~ 4
Clausing, P. , 1986 , On the usefulness of minipigs in toxicology testing of pesticides , Arch. Toxicol 9 (suppl. 1) : 225271 ~
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