書誌事項
- タイトル別名
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- Study on the mechanisms of diarrhea induced by a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.
- シンキ コウ シュヨウヤク エンサン イリノテカン CPT-11 ノ ゲリ ユ
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We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with antidiarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11 -induced delayed diarrhea.
収録刊行物
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- 日本薬理学雑誌
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日本薬理学雑誌 105 (6), 447-460, 1995
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390282679248871936
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- NII論文ID
- 10005706752
- 30034987323
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- NII書誌ID
- AN00198335
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- COI
- 1:CAS:528:DyaK2MXmtlantrs%3D
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- ISSN
- 13478397
- 00155691
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- NDL書誌ID
- 3620387
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- PubMed
- 7557733
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可
