- 著者
- 中野 茂樹 桑田 雅彦 長谷川 浩之 入村 兼司 丸伝 章 森田 健一
- 出版者
- 日本毒性学会
- 雑誌
- The Journal of Toxicological Sciences (ISSN:03881350)
- 巻号頁・発行日
- vol.14, pp.13-59, 1989-10-31
- 被引用文献数
- 3 5
ラットにP-4を2, 10, 50および150mg/kg/dayの投与量で13週間経口投与し, その亜急性毒性ならびに回復性を検討し, 以下の知見を得た. 1. 一般状態の観察では, 50mg/kg/day以上の雌雄各群で投薬後一過性の流涎と主に雌で尿による下腹部の汚染が観察された. その他に重篤な中毒症状はみられず, P-4投与によると思われる死亡例もなかった. 2. 体重は, 雄の50mg/kg/day以上, 雌の150mg/kg/dayの群で増加抑制がみられたが, 摂餌量に著しい変動はなかった. 摂水量は雌雄とも50mg/kg/day以上群で, 投薬初期より明らかな増加を示した. 3. 尿検査では, 50mg/kg/day以上の雌雄各群で尿量の増加, 浸透圧の低下, 蛋白およびウロビリノーゲンの陰性化, さらに電解質排泄量の軽度増加がみられた. 4. 血液学的検査では,150mg/kg/day群の雌雄に赤血球数の増加およびAPTTの短縮, さらに雄ではヘモグロビン量およびヘマトクリット値の増加, 白血球数の減少と雌ではフィブリノーゲン量の増加がいずれも軽度にみられた. 5. 血液生化学的検査では, 雄の50mg/kg/day以上および雌の150mg/kg/dayの群に中性脂肪の減少とγ-GTPおよびAlP活性, および尿素窒素の増加がみられた. さらに雄では総および遊離コレステロール, およびリン脂質が減少し, 雌では総コレステロールの増加およびコリンエステラーゼ活性の減少がみられた. 6. 病理学的検査では, 50mg/kg/day以上の雌雄各群に胸腺および脾臓の肉眼的萎縮がみられたが, 病理組織学的異常は認められなかった. 雄の50mg/kg/day以上および雌の150mg/kg/day群では肝臓重量または重量比が増加し, 病理組織学的検査で肝細胞の肥大および脂肪変性が観察された. 電子顕微鏡検査では, 同群でさらに肝細胞に著明な滑面小胞体の増殖を認めた. 腎臓では, 雄の10mg/kg/day以上, 雌の50mg/kg/day以上の群の近位尿細管上皮細胞内に好酸性の核内封入物を認めたが, その細胞質に腎障害像は全くみられなかった. 7. 回復試験では, P-4投与によるいずれの変化も回復ないし回復傾向を示し, 可逆性の変化であることが示唆された. 8. 無影響量は雄で2mg/kg/day, 雌で10mg/kg/day, 確実中毒量は雄で50mg/kg/day, 雌で150mg/kg/dayと推察された.
1 0 0 0 OA Suxibuzoneの生体内動態(第5報)
- 著者
- 景山 孝正 大野 文俊 安田 行寛 新藤 恭司 三谷 鳴夫 丸伝 章 赤沢 明
- 出版者
- The Japanese Society of Clinical Pharmacology and Therapeutics
- 雑誌
- 臨床薬理 (ISSN:03881601)
- 巻号頁・発行日
- vol.10, no.4, pp.525-533, 1979-12-30 (Released:2010-06-28)
- 参考文献数
- 9
- 被引用文献数
- 1 1
The biological fate of suxibuzone (SB), a new non-steroidal anti-inflammatory agent, was studied in healthy male volunteers with single oral doses and compared with that of phenylbutazone (PB) by a cross-over test, with the following results:1) PB, oxyphenbutazone (Oxy-PB), and γ-hydroxy-phenylbutazone (γ-Hydroxy-PB) were identified in plasma after oral administration of SB. Moreover these metabolites, their glucuronides, SB-glucuronide, 4-hydroxymethyl-phenylbutazone (4-HM-PB)-glucuronide, and p, γ-dihydroxy-phenylbutazone (p, γ-DH-PB) were found in urine.2) Peak plasma concentration of the metabolites was obtained 4 hrs after a single oral dose of 426 mg of SB when the concentration of PB, the main metaboliteof SB, was 36μg/ml, much the same as the corresponding level in the volunteers receiving PB. On the other hand, there was no difference between volunteers receiving SB and PB interms of the concentration of Oxy-PB. But the concentration of γ-Hydroxy-PB was higher after oral SB than after oral PB.3) Urinary excretion of the metabolites was about 8% of the administered dose up to 16 8hrs after oral doses of SB or PB, but in the period shortly after oral doses of SB, Oxy-PB-glucuronide and γ-Hydroxy-PB were excreted to ag reater extent than after oral doses of PB.4) From these results in the plasma and urine after oral doses of SB, it was found that SB may be characterized as a prodrug of PB.5) During the experiment, no side effects or abnormalities were observed in the medical examination and laboratory test except for a slight decrease in the uric acid level in plasma.
- 著者
- 景山 孝正 大野 文俊 安田 行寛 新藤 恭司 三谷 鳴夫 丸伝 章 赤沢 明
- 出版者
- 一般社団法人 日本臨床薬理学会
- 雑誌
- 臨床薬理 (ISSN:03881601)
- 巻号頁・発行日
- vol.10, no.4, pp.525-533, 1979
- 被引用文献数
- 1
The biological fate of suxibuzone (SB), a new non-steroidal anti-inflammatory agent, was studied in healthy male volunteers with single oral doses and compared with that of phenylbutazone (PB) by a cross-over test, with the following results:<BR>1) PB, oxyphenbutazone (Oxy-PB), and γ-hydroxy-phenylbutazone (γ-Hydroxy-PB) were identified in plasma after oral administration of SB. Moreover these metabolites, their glucuronides, SB-glucuronide, 4-hydroxymethyl-phenylbutazone (4-HM-PB)-glucuronide, and <I>p</I>, γ-dihydroxy-phenylbutazone (<I>p</I>, γ-DH-PB) were found in urine.<BR>2) Peak plasma concentration of the metabolites was obtained 4 hrs after a single oral dose of 426 mg of SB when the concentration of PB, the main metaboliteof SB, was 36μg/ml, much the same as the corresponding level in the volunteers receiving PB. On the other hand, there was no difference between volunteers receiving SB and PB interms of the concentration of Oxy-PB. But the concentration of γ-Hydroxy-PB was higher after oral SB than after oral PB.<BR>3) Urinary excretion of the metabolites was about 8% of the administered dose up to 16 8hrs after oral doses of SB or PB, but in the period shortly after oral doses of SB, Oxy-PB-glucuronide and γ-Hydroxy-PB were excreted to ag reater extent than after oral doses of PB.<BR>4) From these results in the plasma and urine after oral doses of SB, it was found that SB may be characterized as a prodrug of PB.<BR>5) During the experiment, no side effects or abnormalities were observed in the medical examination and laboratory test except for a slight decrease in the uric acid level in plasma.