著者

三塩 晋作 廣瀬 徹 中野 純次 松本 純一

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.107, no.8, pp.634-639, 1987-08-25 (Released:2008-05-30)

参考文献数

6

---

A mode of the alkaline and acidic degradation of sodium 6-[D-2-(2-(4-formyl-1-piperazinyl)-5, 8-dihydro-5-oxopyrido [2, 3-d] pyrimidine-6-carboxamido)-p-hydroxyphenylacetamido] penicillanate (1, PL-385) and structures of the degradation products were studied. Treatment of 1 with three equimolar amounts of sodium hydroxide produced a kinetically stable intermediate, (5R)-penicilloic acid (2a), which on kept at 37°C for 65h was converted into a thermodynamically stable product, (5S)-penicilloic acid (2b). Treatment of 1 with an excess of sodium hydroxide gave a deformyl derivative (3) arising from the elimination of formly group via 2. On the acidic treatment of 1, the degradation product, (5R, S)-penilloic acid (4), was yielded.

著者

三塩 晋作 廣瀬 徹 中野 純次 松本 純一

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.107, no.8, pp.607-615, 1987-08-25 (Released:2008-05-30)

参考文献数

11

被引用文献数

1 1

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A series of N-alkylampicillin (2), N-heteroarylampicillin (5) and N-heteroarylcephalexin (6) were synthesized in order to obtain β-lactam detivatives with a broad and orallypotent antibacterial activity similar to that of the injectable N-acylampicillins. 6-[2-[(Pyrido [2, 3-d] pyrimidin-6-yl) methylamino]-2-phenylacetamido] penicillanic acid derivatives (2) were prepared by the reduction of the Schiff base which was derived from the reaction of pyrido [2, 3-d] pyrimidine-6-carboxaldehyde (1) with ampicillin. 6-N-(4-Pyrimidinyl) ampicillin and -cephalexin derivatives (5 and 6) were obtained by the reaction of 4-chloropyrimidine (4) with ampicillin or cephalexin. Compounds 2, 5 and 6 were tested in vitro antibacterial activity and, however, none of them have a broad and potent activity.

著者

三塩 晋作 廣瀬 徹 中野 純次 松本 純一 南 新作

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.107, no.8, pp.592-606, 1987-08-25 (Released:2008-05-30)

参考文献数

11

被引用文献数

1 1

---

A series of N-(pyrido [2, 3-d] pyrimidine-6-carbonyl) ampicillin and -amoxicillin derivatives (1-3) were synthesized and tested for antibacterial activity and acute toxicity in mice. 5, 8-Dihydro-2-(1-piperazinyl)-5-oxopyrido [2, 3-d] pyrimidine-6-carboxylic acid (7) was converted to N-acyl- and -alkylpiperazinyl derivatives (8 and 9) by acylation and alkylation, respectively ; a part of 9 was alternatively prepared by the reactions involving the displacement of N-alkylpiperazines with sulfoxide 11 which was derived from ethyl 5, 8-dihydro-2-methylthio-5-oxopyrido [2, 3-d] pyrimidine-6-carboxylate (10). Treatment of 4, 5, 8 and 9 with ethyl chloroformate followed by the reaction with ampicillin and amoxicillin gave the desired N-acylampicillin (2) and -amoxicillins (1 and 3), respectively. Among compounds 1-3, sodium 6-[D-(-)-2-(2-(4-formyl-1-piperazinyl)-5, 8-dihydro-5-oxopyrido [2, 3-d] pyrimidine-6-carboxamido)-p-hydroxyphenylacetamido] penicillanate (3l, PL-385) was found to be the most excellent in antibacterial activity and to be the less potent in acute toxicity in mice. An alternative route for the synthesis of PL-385 was accomplished, consisting of the reaction of an active ester 13 with amoxicillin. Structure-activity relationships of 1-3 were discussed.

著者

尾崎 幸紘 菅 忠三 吉岡 利紘 森本 悌次郎 原田 正敏

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.110, no.4, pp.268-272, 1990-04-25 (Released:2008-05-30)

参考文献数

12

被引用文献数

1 4

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The present study was carried out to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells. The effects of ether extract of Lithospermi Radix and cultured cells of Lithospermum erythrorhizon SIEB. et ZUCC. and aqueous extract of Coptidis Rizoma and cultured cells of Coptis japonica MAKINO var. dissecta NAKAI on proliferation of granulation tissue in rats were compared. The ether extracts of Lithospermi Radix and the cultured cells enhanced proliferation of granulation tissue by the cotton pellet method. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of shikonin derivatives. On the other hand, the aqueous extracts of Coptidis Rhizoma and the cultured cells inhibited it. The potency of both extract was about the same, if results were compared with the corresponding doses which contained the same quantity of berberine-type alkaloids. From these results, to evaluate an equivalence of pharmacological properties between natural crude drugs and their cultured cells, it is concluded that their qualities and quantities are not so different each other and the almost same pharmacological effect expected on the basis of their uses is required.

著者

長野 一也 東阪 和馬 角田 慎一 堤 康央

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.138, no.7, pp.903-909, 2018 (Released:2018-07-01)

参考文献数

15

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Human epidermal growth factor receptor 2 (Her2)-targeting antibodies and anti-hormone therapy are effective for most breast cancer patients. However, such approaches are not viable with resistant cases or in triple-negative breast cancer (TNBC) patients, given the lack of Her2 and estrogen and progesterone receptors in these patients. Thus, new drug targets are urgently required. From this perspective, we searched for novel drug targets using proteomic analysis, and identified Eph receptor A10 (EphA10), which is elevated in breast cancer cells as compared to normal breast tissue. Here, we evaluated the potential of EphA10 as a drug target by analyzing its protein expression profile/function in cancer cells, and then by using an anti-EphA10 antibody to treat EphA10-expressing tumor-bearing mice. Protein expression profile analysis showed that EphA10 was expressed in various breast cancer subtypes, including TNBCs, with no expression observed in normal tissues, apart from the testes. Moreover, functional analysis of the cancer cells revealed that ligand-dependent proliferation was observed in EphA10-expressed cancer cells. Thus, we developed our novel anti-EphA10 antibody, which binds to EphA10 with high specificity and affinity at the nanomolar level. Finally, therapeutic analysis indicated that tumor growth was significantly suppressed in the mAb-treated mice in a dose-dependent manner. These results suggest that the EphA10-targeting therapy may be a novel therapeutic option for the management of breast cancer, including in TNBCs which aren't currently treated with molecular-targeted agents. Consequently, we hope that these findings will contribute to the development of a new targeting therapy for refractory breast cancer patients.

著者

中村 光浩

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.136, no.4, pp.549-556, 2016 (Released:2016-04-01)

参考文献数

25

被引用文献数

5 9

---

Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

著者

宮本 理人 土屋 浩一郎

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.138, no.7, pp.933-938, 2018-07-01 (Released:2018-07-01)

参考文献数

11

被引用文献数

3 3

---

Sodium-glucose transporter (SGLT)-2 inhibitors, which are currently in clinical use in most of the world, are unique as their hypoglycemic effects are completely independent of insulin action. Potential benefits and indications for the treatment of other diseases like circulatory and renal disorders are attracting attention. SGLT2 inhibitors not only reduce blood glucose levels but also alter the whole-body energy balance to lower body weight, which should result in the amelioration of multiple metabolic disorders like metabolic syndrome. In the symposium, we briefly introduced the physiological as well as biological functions of SGLTs and discussed strategies for drug design by looking back at the history of drug discovery for SGLT2 inhibitors. We also shared our recent data on their combined usage with other hypoglycemic agents and effects on glucagon secretion, which are current clinical topics relevant to SGLT2 inhibitors. Among those topics, strategies for drug discovery of SGLT2 inhibitors are discussed in this review.

著者

高橋 酉蔵 堀 幹夫 浜島 好男

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.78, no.1, pp.6-10, 1958-01-25 (Released:2010-02-19)

参考文献数

18

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For the purpose of elucidating the relationship between effective partial structure of morphine skeleton and analgesic action, several compounds possessing the A-C rings in the morphine skeleton as the basic structure were synthesized. The compounds prepared were 1-dimethylaminoalkyl-1-phenylcyclohexanes (XIII, XVIII, XXV, and XXXII) and 2-dimethylaminoalkyl-2-phenylcyclohexanols (XIV, XXI, XXIX, and XXXV).

著者

近藤 昌夫 藤井 まき子 八木 清仁 渡辺 善照

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.127, no.4, pp.601-609, 2007 (Released:2007-04-01)

参考文献数

47

被引用文献数

1 1

---

Passing of drugs across epithelial cell sheets and endothelial cell sheets is an obligatory step in the absorption of a drug. The passing routes of drugs are classified into transcellular and paracellular pathways. The transcellular route has been widely investigated and is used in clinical therapy. In contrast, drug delivery using the paracellular route has never been fully developed. Sodium caprate is the only absorption-enhancer of drugs that uses the paracellular route. Tight junctions (TJs) exist between adjacent cells in epithelial and endothelial cell sheets, and they play a role in sealing the cell sheets. Therefore, we must modulate the TJ barrier for drug delivery using paracellular route. In this review, we describe barriology, including very recent topics, and overview absorption-enhancers from the perspective of barriology.

著者

須藤 雄気

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.136, no.2, pp.185-189, 2016

---

Retinal proteins possess vitamin A aldehyde (retinal) as a chromophore within seven transmembrane α-helices. Visible light absorption of them triggers <i>trans-cis</i> photoisomerization of the retinal chromophore and induces structural changes in the protein moiety, resulting in a variety of biological functions such as vision, ion transportation, and photosensing. Environmental genomics revealed that retinal proteins are widely distributed through all three biological kingdoms, eukarya, bacteria, and archaea, indicating the biological significance of their light energy conversion. In addition to their biological aspect, retinal proteins have become a focus of interest in part because of applications for optogenetics. On the basis of our results and other findings, we highlight the recent progress in structural and functional studies on retinal proteins.<br>

著者

安本 三治 山下 純一 橋本 貞夫

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.98, no.11, pp.1551-1553, 1978-11-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

6 5

---

Synthesis of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU) (III), which has been found to be a metabolic intermediate of 1, 3-bis (tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU) and an effective antitumor agent, is reported. 1-Alkane- or 1-arene-sulfonyl-5-fluorouracil (I) was trimethylsilylated by treatment with N, O-bis (trimethylsilyl) acetamide and treated with 2-acetoxytetrahydrofuran in the presence of stannic chloride to give 1-alkane- or 1-arene-sulfonyl-3-(tetrahydro-2-furanyl)-5-fluorouracil (II). III was obtained by deblocking of II with methanolic ammonia.

著者

佐藤 大作

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.134, no.2, pp.213-222, 2014

被引用文献数

5

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Circulating counterfeit medicines in the market is a public health threat. Counterfeit medicines become common problem, not only in developing countries, but also in industrialised countries, as internet has made them more accessible. In Japan, the recent survey on the medicines purchased through on-line pharmacy (targeting Japanese consumers) showed that the majority of erectile dysfunction (ED) medicines imported by individuals in Japan were counterfeit version. The survey of Japanese consumers, who privately imported medicines through on-line pharmacy, indicated that 16% of these consumers experienced adverse events associated with these products. Not only that it is just fake brand, but fake medicines may even cause health hazard. The counterfeit version of Avastin recently detected in the United States became a serious threat for those who desperately need these medicines for life-threatening disease. The Japanese regulatory authorities have provided risk information of counterfeit medicines to general public, as well as monitored on-line pharmacies and conducted enforcement action where necessary. However, more resources of compliance activity should be allocated to respond to the situation of growing threats of counterfeit medicines. Purchasing medicines from abroad through unauthorised channel is the major source of counterfeit medicines. It is essential to prevent circulation of counterfeit medicines through international collaboration of various regulatory authorities. To address these problems, the World Health Organization (WHO) has launched a new Member States Mechanism (MSM) to build network of the authorities. Also, INTERPOL (ICPO) initiated globally concerted enforcement actions (Operation Pangea) against pharmaceutical crime as well as built partnership with pharmaceutical industry to create Pharmaceutical Crime Programme. It is also necessary to prevent consumers encountering counterfeit medicines and to prevent health hazard. The Ministry of Health, Labour and Welfare (MHLW) has been actively involved in prevention and educational activities such as public awareness campaign. MHLW started anti-counterfeit medicines and new psychoactive substance project from February 2013, which centrally collects information about counterfeit medicines, in particular, and provides the risk information more effectively to the public. Japanese Government will work together with international community and contribute to combating counterfeiting through public and private partnership.<br>

著者

中尾 英雄 福島 正美 清水 総明 荒川 順生

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.94, no.8, pp.1032-1037, 1974-08-25 (Released:2008-05-30)

参考文献数

6

被引用文献数

12 14

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Water-soluble derivatives of N-(2-chloroethyl)-N-nitrosourea were synthesized and their antitumor activity was tested against leukemia L-1210. Most of these compounds showed a high activity.

著者

中尾 英雄 福島 正美 菅原 眞一

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.93, no.11, pp.1526-1529, 1973-11-25 (Released:2008-05-30)

参考文献数

5

被引用文献数

2 2

---

5-Cyano-2-furaldehyde and its derivatives were synthesized and their antimicrobial activities were tested. Neither series of compound possessed significant antimicrobial activity.

著者

植沢 芳広

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.138, no.2, pp.185-190, 2018-02-01 (Released:2018-02-01)

参考文献数

14

被引用文献数

4

---

Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

著者

関口 富美子

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.125, no.6, pp.491-498, 2005 (Released:2005-06-01)

参考文献数

56

被引用文献数

5 5

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Protease-activated receptors (PARs), a family of G-protein-coupled seven-transmembrane-domain receptors, are activated by proteolytic unmasking of the N-terminal cryptic tethered ligand by certain serine proteases. Among four PAR family members cloned to date, PAR-1, PAR-2, and PAR-4 can also be activated through a non-enzymatic mechanism, which is achieved by direct binding of exogenously applied synthetic peptides based on the tethered ligand sequence, known as PARs-activating peptides, to the body of the receptor. Various peptide mimetics have been synthesized as agonists for PARs with improved potency, selectivity, and stability. Some peptide mimetics and/or nonpeptide compounds have also been developed as antagonists for PAR-1 and PAR-4. PARs are widely distributed in the mammalian body, especially throughout the alimentary systems, and play various roles in physiological/pathophysiological conditions, i.e., modulation of salivary, gastric, or pancreatic glandular exocrine secretion, gastrointestinal smooth muscle motility, gastric mucosal cytoprotection, suppression/facilitation of visceral pain and inflammation, etc. Thus PARs are now considered novel therapeutic targets, and development of selective agonists and/or antagonists for PARs might provide a novel strategy for the treatment of various diseases that are resistant to current therapeutics.

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

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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

才川 勇 高井 明 中島 良文 吉田 長作 保田 隆 清水 悦郎 酒井 広志 滝 秀雄 田井 賢 高下 寛

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.97, no.10, pp.1071-1081, 1977-10-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

5 3

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Metabolism of 6-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) phenylacetamido] penicillanic acid (T-1220), a new β-lactam antibiotic, was studied in vivo and in vitro. Only unchanged T-1220 was detected by bioautography in urine of human, monkeys, dogs, rats, and mice receiving T-1220 intramuscularly. When 14C-labeled T-1220 was administered to rats, most of the radioactive product was excreted unchanged in the urine, but two metabolites were detected in a minute amount by autoradiography. These metabolites were identified as 14C-labeled α-{3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido}-benzylpenicillin (14C-T-1220A) and 14C-labeled α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido) benzylpenicilloic acid (14C-T-1220B) by thin-layer chromatography, electrophoresis, and high-pressure liquid chromatography. Metabolism of 14C-T-1220 and its mechanism were studied by using high-pressure liquid chromatography for the separation and radioactive measurement for the determination. In the case of the intramuscular administration of 14C-T-1220 to rats, about 92% of the radioactivity was excreted unchanged in urine and bile, but about 94% of the radioactivity in the feces was 14C-T-1220B. The same results were found in rats pretreated with SKF-525A and phenobarbital. In situ studies showed that 14C-T-1220 changed to 14C-T-1220B in the intestinal tracts, and in vitro studies showed that 14C-T-1220 changed to 14C-T-1220B in fecal homogenate. From these results, it seemed that 14C-T-1220 was changed to 14C-T-1220B by β-lactamase produced from intestinal flora.

著者

石津 利作

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

no.335, pp.1-12, 1910-01-26

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純粹度ヲ保シ難キ製品ニ就キ極メテ不確實ナル分析ヲ基礎トシテC_<16>H_<19>O_4SK+H_2Oナル化學記號ヲ設定スルハ大早計ナルヲ難シ純レスピラチン」ナルモノニ於テ喜多尾氏カ言明セルカ如キ特殊ノ形熊並ニ性状ヲ發見スルコト能ハサルヲ述へ同氏ガ「デブス氏法ニ依リテ硫黄ヲ定量シ其成績ニ甚シキ動揺アルハ偶々以テ自己技術ノ拙劣ヲ表ハスモノニシテ未タ純レスピラチン中硫黄定量ノ困難ナル證據トナスニ足ラサルヲ論シ終ニ藥學雜誌上ニ發表セラレタルカ如ク「チオヂクレオソール」ナル名稱ハ單ニ發明名稱ニシテ此名稱ニ依リ純レスピラチン」ノ分子構造ヲ表示セントスル意ニ非スシテ只其成分ノ列記ニ過キサルコトヲ齊シク他ノ雜誌並ニ新聞ニ廣古シ世人ヲ惑ハスカ如キ告白ヲ避ケ且ツ硫黄含量ノ確定スルニ至ル迄C_<16>H_<19>O_4SK+H_2Oノ如キ更ニ根據ナキ化學記號ヲ吹聽スルノ輕學ヲ戒メラレンコトヲ發明者ニ希望セリ

著者

川口 安郎 中村 芳正 佐藤 俊幸 武田 節夫 丸中 照義 藤井 節郎

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.98, no.4, pp.525-536, 1978-04-25 (Released:2008-05-30)

参考文献数

14

被引用文献数

5 8

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After oral administration of 5-fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), the level of 5-fluoro-2, 4-pyrimidinedione (5-FU) was 5 to 7 times higher in the plasma and normal tissues and 8 to 12 times in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). Moreover, these levels were maintained longer than after administration of FT. In tumor tissue, the concentration of 5-FU was still as high as 1.42 μg/g 12 hr after administration of FD-1. FD-1 was degraded to 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) by liver microsomal drug-metabolizing enzymes in vitro and to FT spontaneously. Subsequently, FT was converted enzymically to the active substance, 5-FU, and 3-FT changed to 5-FU spontaneously. Conversion of FD-1 to 5-FU via 3-FT was greater than via FT. It is concluded that a large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. γ-Hydroxybutyric acid was found to be formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.