- 著者
- 多比良 和基 安田 行寛 新藤 恭司 三谷 鳴夫 赤沢 明
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.100, no.3, pp.272-279, 1980-03-25 (Released:2008-05-30)
- 参考文献数
- 19
- 被引用文献数
- 2 2
The biological fate of 4-butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione : suxibuzone (SB) was studied in rats and beagle dogs. Furthermore, the effects of SB on liver microsomal drug metabolizing enzyme systems in rats were compared with those of phenylbutazone (PB), after daily oral administration of SB or PB for 1 week. 1) The biological fate of SB was different in rats and dogs and in the former a sex difference was noted. 2) Liver microsomal drug metabolizing enzyme systems were induced especially in male. 3) No difference between the two drugs was noted. However, when a single oral dose of SB was administered, keeping the PB schedule the same as above, the plasma half-life of PB was markedly shortened and maximum plasma levels of metabolites were rapidly reached. These results suggest that the biological fate of SB was stimulated by the enhancement or induction of liver microsomal drug metabolizing enzyme systems due to PB and its metabolites after daily oral administration.
- 著者
- 新藤 恭司 安田 行寛 多比良 和基 三谷 鳴夫 神田 敦弘 赤沢 明
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.12, pp.1186-1200, 1979-12-25 (Released:2008-05-30)
- 参考文献数
- 20
- 被引用文献数
- 4 5
The biological fate of 4-butyl-4-(β-carboxypropionyl-oxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. The results obtained were as follows ; 1) When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and γ-hydroxyphenylbutazone (γ-Hydroxy-PB) in all species, though species differences were observed in the maximum plasma levels of the respective metabolites. Only in dogs and monkeys, was a small amount of SB detected in the plasma during the early time of dosing. 2) The metabolites and their maximum levels in plasma after the administration of SB were almost identical with those observed after the administration of PB. 3) After administration of SB, the main metabolites found in urine were PB, Oxy-PB, γ-Hydroxy-PB and their conjugates in all species, while species differences were observed in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was observed in small amount for 0-12 hours. 4) There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. 5) Differences between male and female in maximum plasma levels of PB and γ-Hydroxy-PB and in urinary excreted percent of γ-Hydroxy-PB were observed only in rats. 6) Species differences were observed in esterase activity on SB in vitro. 7) SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. 8) SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB and γ-Hydroxy-PB had no effect on its action.
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
- 藤井 節郎 奥田 拓道 赤沢 明 安田 行寛 川口 安郎 福永 育史 西川 栄郎
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 薬学雑誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.95, no.6, pp.732-740, 1975
- 被引用文献数
- 5
In order to investigate the fate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) in comparison with that of 5-fluorouracil tritiated FT-207 (<SUP>3</SUP>H-FT-207) and 5-fluovouracil (<SUP>3</SUP>H-5-fluorouracil)were administered from the rectum in normal and AH-130 tumor-bearing rats, and rapid absorption of <SUP>3</SUP>H-FT-207 or <SUP>3</SUP>H-5-fluorouracil, was observed. Blood level of radioactivity after rectal administration of <SUP>3</SUP>H-FT-207 was higher and more continuous than that of <SUP>3</SUP>H-5-fluorouracil. Although the radioactivity after rectal administration of <SUP>3</SUP>H-FT-207 and <SUP>3</SUP>H-5-fluovouracil was widely distributed in the various tissues of the animal with or without tumor, the highest concentration of the radioactivity was observed in the kidneys, and higher in tumor. The radioactivity in lymphatic gland reached a maximum level within 2-4 hr after the rectal administration of <SUP>3</SUP>H-FT-207 and declined very slowly. The urinary excretion of radioactivity within 24 hr was about 30% of the administered dose of <SUP>3</SUP>H-FT-207. More than 85% of the excreted radioactivity accounted for FT-207 and its metabolite, α-fluoro-β-alanine. Other metabolites such as 5-fluorouracil, α-fluoro-β-ureidopropionic acid and tritiated water were detected in small amounts in rat urine. The radioactivity in blood and tumor, 4 hr after rectal administration of <SUP>3</SUP>H-FT-207, was found to represent FT-207. However, the radioactivity in liver was due to the presence of α-fluoro-β-alanine. About 90% radioactivity in lymphatic gland within 2-6 hr after rectal administration of <SUP>3</SUP>H-FT-207 was detected as FT-207.
- 著者
- 安田 行寛 東郷 常夫 采見 憲男 渡辺 昭治 播磨 耕介 鈴江 崇志
- 出版者
- 公益社団法人 日本化学療法学会
- 雑誌
- CHEMOTHERAPY (ISSN:00093165)
- 巻号頁・発行日
- vol.21, no.6, pp.1171-1178, 1973-08-25 (Released:2011-03-08)
- 参考文献数
- 9
- 被引用文献数
- 1
N1-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207), a new antimetabolic anticancer agent synthesized in USSR, was studied on antimicrobial activity in vitro and distribution, excretion and metabolism in vivo.The results obtained were as follows.1) Antimicrobial activityFT-207 showed fairly active against Micrococcus flavus ATCC 10240, Sarcina lutea PCI 1001, Staphylococcus epidermidis and Staphylococcus aureus 209 P, but in general the activity was inferior to that of 5-FU.2) DistributionBy the intravenous administration of FT-207, 400mg/kg, in normal and AH-130 bearing rats, the concentration of FT-207 in serum and tissues maintained measurably until 16-24 hours.On the other hand, the active substances (5-FU, etc.) from FT-207 detected at 1-4 hours and peaked at 4-16 hours in tissues.3) Urinary excretionFT-207 and its active substances were excreted in urine for a long time, and the recoveries of FT-207 for 48 hours in rats, mice and rabbits were 12-18%.4) MetabolismIn normal and AH-130 bearing rats, the main active substance from FT-207 administrated intravenously was 5-FU.
- 著者
- 安田 行寛 東郷 常夫 采見 憲男 渡辺 昭治 播磨 耕介 鈴江 崇志
- 出版者
- 公益社団法人 日本化学療法学会
- 雑誌
- 日本化学療法学会雑誌 (ISSN:00093165)
- 巻号頁・発行日
- vol.21, no.6, pp.1171-1178, 1973
N<SUB>1</SUB>-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207), a new antimetabolic anticancer agent synthesized in USSR, was studied on antimicrobial activity <I>in vitro</I> and distribution, excretion and metabolism <I>in vivo</I>.<BR>The results obtained were as follows.<BR>1) Antimicrobial activity<BR>FT-207 showed fairly active against <I>Micrococcus flavus</I> ATCC 10240, <I>Sarcina lutea</I> PCI 1001, <I>Staphylococcus epidermidis</I> and <I>Staphylococcus aureus</I> 209 P, but in general the activity was inferior to that of 5-FU.<BR>2) Distribution<BR>By the intravenous administration of FT-207, 400mg/kg, in normal and AH-130 bearing rats, the concentration of FT-207 in serum and tissues maintained measurably until 16-24 hours.<BR>On the other hand, the active substances (5-FU, <I>etc</I>.) from FT-207 detected at 1-4 hours and peaked at 4-16 hours in tissues.<BR>3) Urinary excretion<BR>FT-207 and its active substances were excreted in urine for a long time, and the recoveries of FT-207 for 48 hours in rats, mice and rabbits were 12-18%.<BR>4) Metabolism<BR>In normal and AH-130 bearing rats, the main active substance from FT-207 administrated intravenously was 5-FU.
- 著者
- 藤井 節郎 奥田 拓道 赤沢 明 安田 行寛 川口 安郎 福永 育史 西川 栄郎
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.95, no.6, pp.732-740, 1975-06-25 (Released:2008-05-30)
- 参考文献数
- 13
- 被引用文献数
- 4 5
In order to investigate the fate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) in comparison with that of 5-fluorouracil tritiated FT-207 (3H-FT-207) and 5-fluovouracil (3H-5-fluorouracil)were administered from the rectum in normal and AH-130 tumor-bearing rats, and rapid absorption of 3H-FT-207 or 3H-5-fluorouracil, was observed. Blood level of radioactivity after rectal administration of 3H-FT-207 was higher and more continuous than that of 3H-5-fluorouracil. Although the radioactivity after rectal administration of 3H-FT-207 and 3H-5-fluovouracil was widely distributed in the various tissues of the animal with or without tumor, the highest concentration of the radioactivity was observed in the kidneys, and higher in tumor. The radioactivity in lymphatic gland reached a maximum level within 2-4 hr after the rectal administration of 3H-FT-207 and declined very slowly. The urinary excretion of radioactivity within 24 hr was about 30% of the administered dose of 3H-FT-207. More than 85% of the excreted radioactivity accounted for FT-207 and its metabolite, α-fluoro-β-alanine. Other metabolites such as 5-fluorouracil, α-fluoro-β-ureidopropionic acid and tritiated water were detected in small amounts in rat urine. The radioactivity in blood and tumor, 4 hr after rectal administration of 3H-FT-207, was found to represent FT-207. However, the radioactivity in liver was due to the presence of α-fluoro-β-alanine. About 90% radioactivity in lymphatic gland within 2-6 hr after rectal administration of 3H-FT-207 was detected as FT-207.
- 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.
- 著者
- 新藤 恭司 安田 行寛 多比良 和基 三谷 鳴夫 神田 敦弘 赤沢 明
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 藥學雜誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.99, no.12, pp.1186-1200, 1979
- 被引用文献数
- 5
The biological fate of 4-butyl-4-(β-carboxypropionyl-oxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. The results obtained were as follows ; 1) When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and γ-hydroxyphenylbutazone (γ-Hydroxy-PB) in all species, though species differences were observed in the maximum plasma levels of the respective metabolites. Only in dogs and monkeys, was a small amount of SB detected in the plasma during the early time of dosing. 2) The metabolites and their maximum levels in plasma after the administration of SB were almost identical with those observed after the administration of PB. 3) After administration of SB, the main metabolites found in urine were PB, Oxy-PB, γ-Hydroxy-PB and their conjugates in all species, while species differences were observed in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was observed in small amount for 0-12 hours. 4) There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. 5) Differences between male and female in maximum plasma levels of PB and γ-Hydroxy-PB and in urinary excreted percent of γ-Hydroxy-PB were observed only in rats. 6) Species differences were observed in esterase activity on SB in vitro. 7) SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. 8) SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB and γ-Hydroxy-PB had no effect on its action.