雑誌文献を検索します。書籍を検索する際には「書籍検索」を選択してください。

Brain and Nerve No to Shinkei Volume 43, Issue 9 （September 1991）

Brain and Nerve 脳と神経 43巻9号（1991年9月発行）

Japanese English

原著

犬髄腔内ACNUの動態解析—HPLCとautoradiographyによる検討 Intrathecal Distribution of ACNU by Various Modes of its Administration Analyzed by HPLC and Autoradiography 堀智勝 ¹ , 平尾順 ¹ , 岡本久代 ¹ , 西山誠 ¹ , 田中聰 ¹ , 村岡浄明 ¹ , 田淵二三枝 ² , 龍原徹 ² , 中島栄一 ³ Tomokatsu Hori ¹ , Jun Hirao ¹ , Hisayo Okamoto ¹ , Makoto Nishiyama ¹ , Satoshi Tanaka ¹ , Kiyoaki Muraoka ¹ , Fumie Tabuchi ² , Tohru Tatsuhara ² , Eiichi Nakajima ³ ¹鳥取大学医学部脳幹研究施設外科 ²鳥取大学医学部病院薬剤部 ³三共株式会社研究所分析代謝研究室 ¹Division of Neurosurgery, Institute of Neurological Sciences, Tottrori University School of Medicine ²Department of Hospital Pharmacy, Tottori University Hospital ³Division of Analytical and Metabolic Research Laboratories, Sankyo Co. キーワード： ACNU , intrathecal , HPLC , autoradiography Keyword: ACNU , intrathecal , HPLC , autoradiography pp.833-841

発行日 1991年9月1日 Published Date 1991/9/1

DOI https://doi.org/10.11477/mf.1406900242

PDF(10923KB)

有料閲覧

Abstract 文献概要
1ページ目 Look Inside

　悪性脳腫瘍の髄膜播種症が近年増加傾向にある。その治療の1つとしてACNUの髄腔内投与が考えられる。雑種成犬腰部1回5mg投与では脊髄腔に豊富な薬剤がみられるが，大槽内ではHPLC法でも検出域値以下であった。大槽1回注入では腰部への移行はin vitroでのグリオーマ細胞90％成長抑制条件（10μg／ml；30min以上）を満足する濃度に達したが，注入初期で大槽部に高濃度の薬剤が検出され副作用が問題となる。さらに脳室へはほとんど移行がみられなかった。脳室1回注入では腰部に充分な薬剤が認められず，治療としては満足できないと考えられた。脳室—腰部灌流法では大槽でも腰部でも上記in vitroの有効薬剤濃度が達成され，脳表には有効な薬剤濃度がみられないものの，試みた範囲では最良の治療法と考えられた。臨床応用する場合，脳室—腰部ACNU灌流法が現時点で有用な治療法と考えられるが，有効な治療効果を得るには髄液内ACNUの計測が必要と考えられる。

Various modes of administration of ACNU (nimustine hydrochloride) were tried to make clear which mode is the best method to obtain intrathecal diffuse distribution of ACNU to match the condition of killing of glioma cells (10μg/ml ; > 30min.). Tried modes of administration included 1) bolus injection into ventricular cavity, 2) bolus injection into cisterna magna, 3) bolus injection into lumbar subarachnoid space, 4) ventriculo-lumbar perfusion, 5) chiasmatic cistern-lumbar perfusion. Used dose of ACNU was 5mg/body for all modes of adminis-tration. ACNU level in CSF was measured by HPLC method specially developed by authors. To make clear intrathecal distribution of ACNU, autoradio-graphy using 14C-ethylene-ACNU was studied after administration of 10μCi/Kg of radioactive ACNU. The images were studied by image analyzer system (BAS-2,000 system developed by Fuji Film Co. Ltd). Among the modes of administration tried, ventriculo-lumbar perfusion method gave the best results in terms of lumbar, ventricular, cisterna magna, and basal cistern distribution of ACNU to match the cell kill condition experimentally ascer-tained. Although, bolus injection of ACNU into cisterna magna gave sufficient amount of ACNU in lumbar region, the initial level of ACNU was too high in cisterna magna, and administration of ACNU onece a week for three times in a canine cisterna magna resulted in considerable deteriora-tion of brain stem and basal structure. In addition to it, the level of ACNU in ventricular cavity was not detectable. Lumbar bolus injection resulted in also too much ACNU accumulation at the injected lum-bar area, and at the cisterna magna region, ACNU was not detectable.

Chiasmatic-lumbar perfusion method resulted in poor distribution of the drug at the cisterna magna and lumbar region. Autoradiographic pictures of lumbar bolus injection, cisterna magna bolus injec-tion, ventriculo-lumbar perfusion, and chiasmatic cistern-lumbar perfusion gave sufficient imforma-tion of drug distribution for clinical application.