Plasma, Intestine and Tumor Levels of 5-Fluorouracil in Mice Bearing L1210 Ascites Tumor Following Oral Administration of 5-Fluorouracil, UFT(Mixed Compound of Tegafur and Uracil), Carmofur and 5'-Deoxy-5-fluorouridine
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概要
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Several 5-fluorouracil (5-FU) derivatives, 1-hexylcarbamoyl-5-fluorouracil (HCFU), 5'-deoxy-5-fluorouridine (5'-DFUR) and UFT (mixed compound of tegafur and uracil), have been developed and clinically widely used. However, comparative pharmacokinetic studies of the parent compound and other fluorinated drivatives have not been precisely reported. The dosage of the oral clinical use for human cancer of 5-FU, HCFU, 5'-DFUR and UFT as tegafur (FT) is 200-300mg/d, 600mg/d, 800-1200mg/d and 300-600mg/d respectively. These amounts of the drugs are almost equimolar. Previously, we reported the effect of oral equimolar administration of each four drugs on thymidilate synthase activity, deoxyribonucleotide metabolism and cell cycle progression in L1210 ascites tumor.^<1, 2)> In this study, we examined the antitumor effect and 5-FU concentration in the plasma, intestine and tumor after oral equimolar administrations of each drug using BDF1 mice bearing L1210 ascites tumor. In our study, UFT showed the best life prolongation among these four drugs. The intestine 5-FU level was highest by treatment with 5-FU during the initial 4h. The plasma 5-FU level was highest by treatment with HCFU for 4h. But the tumor 5-FU level was highest by treatment with UFT over the 24h. In spite of the high plasma 5-FU concentration after the treatment with HCFU, the 5-FU concentration in the tumor was below the detectable level until 24h. These findings suggested that the highest specific accumulation of 5-FU in tumor cells may explain the best therapeutic results of UFT.
- 公益社団法人日本薬学会の論文
- 2001-11-01
著者
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KAGAWA Yoshiyuki
Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University
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SAKURAI MINORU
Department of Orthopaedic Surgery, School of Medicine, Tohoku University
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OOI Kazuya
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Josai University
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KOJIMA Michio
Department of Hospital Pharmacy, Mie University School of Medicine
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Sakurai Minoru
Department Of Pediatrics Mie University School Of Medicine
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Kawasaki Hajime
Department Of Pediatrics Mie University School Of Medicine
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Kawasaki Hajime
Department Of Pediatrics
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Kagawa Yoshiyuki
Department Of Clinical Pharmaceutics And Pharmacy Practice Faculty Of Pharmaceutical Sciences Univer
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Kagawa Yoshiyuki
Department Of Pharmacy Mie University School Of Medicine
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Ooi Kazuya
Department Of Pharmacy Yokkaichi Social Insurance Hospital
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Ooi Kazuya
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Josai University
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Kojima M
Department Of Hospital Pharmacy Mie University School Of Medicine
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Kojima Michio
Department Of Pharmacy Mie University School Of Medicine
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HIGASHIGAWA MASAMUNE
Department of Pediatrics, Mie University School of Medicine
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KAKITO HIDESHI
Department of Hospital Pharmacy, Mie University School of Medicine
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OHKUBO Toshiki
Department of Pediatrics, Mie University School of Medicine
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Higashigawa M
Mie Univ. Mie Jpn
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Higashigawa Masamune
Department Of Pediatrics Mie University School Of Medicine
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Ohkubo Toshiki
Department Of Pediatrics Mie University School Of Medicine
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Kojima Michio
Department Of Hospital Pharmacy Mie University School Of Medicine
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Sakurai Minoru
Department Of Biomolecular Engineering Tokyo Institute Of Technology
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Kagawa Yoshiyuki
Department of Clinical Pharmaceutics & Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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