抗悪性腫瘍薬,塩酸ドキソルビシンで誘発されるイヌの遅延性嘔吐  [in Japanese] Delayed emesis induced by the chemotherapeutic agent doxorubicin hydrochloride in dogs  [in Japanese]

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Abstract

イヌを用い,非プラチナ性抗悪性腫瘍薬,塩酸ドキソルビシン(ドキソルビシン)によって投与後24時間以降に誘発される遅延性嘔吐の発現を検討し,併せて摂餌量,摂水,排便行動などに及ぼす影響を検討した. 2mg/kgのドキソルビシンを静脈内投与すると,投与24時間以内に発現する急性嘔吐は少なかったが,投与24時間以降に発現する遅延性の嘔吐が全例に誘発された.この遅延性嘔吐の発現は投与3∼4日目にピークに達し,5日目には減少した.遅延性嘔吐の発現にやや遅れて摂餌量および飲水回数の減少,排便回数の増加が観察された.5-HT<SUB>3</SUB>受容体拮抗薬である塩酸アザセトロン(アザセトロン)の0.3および1mg/kg/dayを抗悪性腫瘍薬投与の24時間後から4日間反復経口投与すると,ドキソルビシン誘発の遅延性嘔吐をそれぞれ約30および50%減少させた.ドキソルビシンで誘発される遅延性嘔吐の発現機序には,一部5-HT<SUB>3</SUB>受容体が関与していると推察される.摂餌量および飲水回数の減少に対しては,アザセトロンは明らかな影響を及ぼさなかったが,排便回数の増加に対しては改善作用を示した.イヌにドキソルビシンを投与する本法は,非プラチナ性抗悪性腫瘍薬で誘発される遅延性咽吐のモデルとして,機序の解明および治療薬の開発に有用と考えられる.

The occurrence of delayed emesis induced 24 h after the administration of a non-platina chemotherapeutic agent, doxorubicin hydrochloride (doxorubicin), as well as behaviors such as feeding, drinking and defecation were examined in dogs. A single intravenous administration of 2 mg/kg doxorubicin induced emesis within 24 h of administration in some dogs, while delayed emesis was observed 24 h after administration in all dogs. This delayed emesis emerged strongly at day 3 or 4 and decreased at day 5. Hypophagia, the decreased frequency of drinking and the increased frequency of defecation were induced shortly after delayed emesis. Twenty-four hours after the administration of doxorubicin, a daily dose of 0.3 and 1 mg/kg/ day, p.o. azasetron, a 5-HT<SUB>3</SUB> antagonist, was administered for 4 days. Doxorubicin-induced delayed emesis was observed to decrease by about 30 and 50%, respectively. This result suggests that 5-HT<SUB>3</SUB> receptors play a role in the mechanism of delayed emesis. Azasetron was found to improve the increased frequency of defecation, but exerted no obvious effect on hypophagia or on the decreased frequency of drinking. Taken together, we suggest that doxorubicin-induced emesis in dogs is a useful method to study further the mechanisms of delayed emesis and to investigate novel therapeutic agents against delayed emesis.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 116(5), 313-320, 2000-11-01

    The Japanese Pharmacological Society

References:  24

Codes

  • NII Article ID (NAID)
    10008181341
  • NII NACSIS-CAT ID (NCID)
    AN00198335
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    00155691
  • NDL Article ID
    5539934
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z19-247
  • Data Source
    CJP  NDL  J-STAGE 
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