腹腔注射CPT-11后，无胸腺小鼠肠道和血浆中腹泻的发生与CPT-11的活性代谢产物SN-38浓度之间的关系。
Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11.
作者信息
Araki E, Ishikawa M, Iigo M, Koide T, Itabashi M, Hoshi A
机构信息
Department of Clinical Pathology, National Cancer Center Hospital, Tokyo.
出版信息
Jpn J Cancer Res. 1993 Jun;84(6):697-702. doi: 10.1111/j.1349-7006.1993.tb02031.x.
Abstract
Severe diarrhea occurred during daily intraperitoneal administration of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) at a dose of 50 mg/kg in athymic mouse. Serial determination of CPT-11 and 7-ethyl-10-hydroxycamptothecin (SN-38), with the use of an on-line solid extraction HPLC system, demonstrated that much higher levels of the compounds are retained in the intestine and the blood plasma after five consecutive daily injections than after a single injection. Histologic examination of the gastrointestinal tract showed hemorrhagic colitis on day 7 and later after five consecutive daily injections of CPT-11. The direct cause of diarrhea associated with CPT-11 administration is considered to be enterocolitis caused by high levels of SN-38 and/or CPT-11 retained for a long period in the intestine.
摘要
在无胸腺小鼠中，每日腹腔注射剂量为50mg/kg的7-乙基-10-[4-(1-哌啶基)-1-哌啶基]羰基氧喜树碱（CPT-11）时出现了严重腹泻。使用在线固相萃取高效液相色谱系统对CPT-11和7-乙基-10-羟基喜树碱（SN-38）进行连续测定，结果表明，连续每日注射五次后，肠道和血浆中这些化合物的保留水平比单次注射后高得多。对胃肠道进行组织学检查发现，连续每日注射五次CPT-11后第7天及之后出现了出血性结肠炎。与CPT-11给药相关的腹泻的直接原因被认为是由于SN-38和/或CPT-11在肠道中长期高水平保留而导致的小肠结肠炎。
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Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11.腹腔注射CPT-11后，无胸腺小鼠肠道和血浆中腹泻的发生与CPT-11的活性代谢产物SN-38浓度之间的关系。
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