Skip to main content
SpringerLink
Log in

Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1∶4 tegafur and uracil combination

  • Original Articles
  • UFT, Gastric Cancer Postoperative Prescription
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1∶4, were examined in 26 patients with macroscopic State I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28±26.88, 4.41±1.78, and 0.51±0.20 μg h ml−1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anttila MI, Sotaniemi EA, Kairaluoma MI, Mokka RE, Sundquist HT (1983) Pharmacokinetics of futrafur after intravenous and oral administration. Cancer Chemother Pharmacol 10: 150

    Google Scholar 

  2. Armbrecht U, Lundell L, Lindstedt G, Stockbruegger RW (1988) Causes of malabsorption after total gastrectomy with Roux-en-Y reconstruction. Acta Chir Scand 154: 37

    Google Scholar 

  3. Benvenuto JA, Lu K, Hall SW, Benjamin RS, Loo TL (1978) Disposition and metabolism of 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) in humans. Cancer Res 38: 3867

    Google Scholar 

  4. Bronk JR, Lister N, Lynch S (1987) Absorption of 5-fluorouracil and related pyrimidines in rat small intestine. Clin Sci 72: 705

    Google Scholar 

  5. Fujii S, Ikenaka K, Fukushima M, Shirasaka T (1978) Effect of uracil and its derivatives on antitumor activity of 5-fluorouracil and 1-(2-tetrahydrofuryl)-5-fluorouracil. Jpn J Cancer Res 69: 763

    Google Scholar 

  6. Fujii S, Kitano S, Ikenaka K, Shirasaka T (1979) Effect of coadministration of uracil or cytosine on the antitumor activity of clinical doses of 1-(2-tetrahydrofuryl)-5-fluorouracil and level of 5-fluorouracil in rodents. Jpn J Cancer Res 70: 209

    Google Scholar 

  7. Gibaldi M, Perrier D (eds) (1982) Pharmacokinetics. Marcel Dekker, New York

    Google Scholar 

  8. Hanaue H, Kurosawa T, Kitano Y, Miyakawa S, Nemoto A, Yamamoto H, Asagoe T, Takada T, Yasuda H, Shikata J (1987) Anticancer drug distribution in lymph and blood during adjuvant chemotherapy after surgery for gastric carcinoma. A study with a combined preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil. Cancer 59: 1571

    Google Scholar 

  9. Ikenaka K, Shirasaka T, Kitano S, Fujii S (1979) Effect of uracil on metabolism of 5-fluorouracil in vitro. Jpn J Cancer Res 70: 353

    Google Scholar 

  10. Kimura K, Suga S, Shimaji T, Kitamura M, Kubo K, Suzuoki Y, Isobe K (1980) Clinical basis of chemotherapy for gastric cancer with uracil and 1-(2′-tetrahydrofuryl)-5-fluorouracil. Gastroenterol Jpn 15: 119

    Google Scholar 

  11. Maehara Y, Nagayama S, Okazaki H, Nakamura H, Shirasaka T, Fujii S (1981) Metabolism of 5-fluorouracil in various human normal and tumor tissues. Jpn J Cancer Res 72: 824

    Google Scholar 

  12. Maehara Y, Kusumoto T, Kusumoto H, Anai H, Sugimachi K (1988) UFT is more antineoplastic against gastric carcinoma than 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil and 1-hexylcarbamoyl-5-fluorouracil. Chemotherapy 34: 484

    Google Scholar 

  13. Maehara Y, Kusumoto T, Kusumoto H, Anai H, Sakaguchi Y, Kido Y, Okamura T, Korenaga D, Sugimachi K (1989) 5-Fluorouracil and UFT-sensitive gastric carcinoma has a high level of thymidylate synthase. Cancer 63: 1693

    Google Scholar 

  14. Maehara Y, Sakaguchi Y, Kusumoto T, Kusumoto H, Sugimachi K (1989) Potentiation of 5-fluorouracil cytotoxicity by combining hyperthermia and dipyridamole in vitro. Anticancer Res 9: 967

    Google Scholar 

  15. Maehara Y, Watanabe A, Kakeji Y, Baba H, Kohnoe S, Sugimachi K (1990) Postgastrectomy prescription of mitomycin C and UFT for patients with stage IV gastric carcinoma. Am J Surg 160: 242

    Google Scholar 

  16. Maehara Y, Moriguchi S, Emi Y, Watanabe A, Kohnoe S, Tsujitani S, Sugimachi K (1990) Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas. Cancer 66: 156

    Google Scholar 

  17. Maehara Y, Sugimachi K, Akagi M, Kakegawa T, Shimazu H, Tomita M (1992) Early postoperative chemotherapy following noncurative resection for patients with advanced gastric cancer. Br J Cancer 65: 413

    Google Scholar 

  18. Maehara Y, Takahashi I, Yoshida M, Emi Y, Baba H, Kusumoto H, Kohnoe S, Sugimachi K (1992) Metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in partially hepatectomized rats. Anti-cancer Drugs 3: 117

    Google Scholar 

  19. Marunaka T, Umeno Y (1978) Quantitative determination of 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione and its metabolites in plasma by high-pressure liquid chromatography and gas chromatography-mass fragmentography. J Chromatogr 157: 321

    Google Scholar 

  20. Marunaka T, Umeno Y, Yoshida K, Nagamachi M, Minami Y, Fujii S (1980) High-pressure liquid chromatographic determination of ftorafur [1-(tetrahydro-2-furanyl)-5-fluorouracil] and GLC-mass spectrometric determination of 5-fluorouracil and uracil in biological materials after oral administration of uracil plus ftorafur. J Pharm Sci 69: 1296

    Google Scholar 

  21. Ohsawa S, Kondo Y, Shiroto H, Masuko H, Fukushima T, Kataoka A, Ohmori K, Sawaguchi Y, Baba E, Takahashi T, Sawada Y, Hashimoto I, Uchino J (1992) A study of urinary tegafur, 5-fluorouracil (5-FU) and uracil concentrations in the case of gastric carcinoma for the confirmation of drug-taking compliance after UFT oral administration (in Japanese with English abstract). Jpn J Cancer Chemother 19: 2189

    Google Scholar 

  22. Ota K, Taguchi T, Kimura K (1988) Report on nationwide pooled data and cohort investigation in UFT phase II study. Cancer Chemother Pharmacol 22: 333

    Google Scholar 

  23. Reeves WJ, Cailleau R (1969) Mechanism of growth inhibition by 5-flurouracil. Reversal studies with pyrimidine metabolites in vitro (34041). Proc Soc Exp Biol Med 131: 1068

    Google Scholar 

  24. Rieu PNMA, Jansen JBMJ, Joosten HJM, Lamers CBHW (1990) Effect of gastrectomy with either Roux-en-Y or Billroth II anastomosis on small-intestinal function. J Gastroenterol 25: 185

    Google Scholar 

  25. Sasaki H, Nakamura J, Konishi R, Shibasaki J (1986) Intestinal absorption characteristics of 5-fluorouracil, ftorafur and 6-mercaptopurine in rats. Chem Pharm Bull (Tokyo) 34: 4265

    Google Scholar 

  26. Schanker LS, Tocco DJ (1960) Active transport of some pyrimidines across the rat intestinal epithelium. J Pharmacol Exp Ther 128: 115

    Google Scholar 

  27. Shimoyama T, Mikawa K, Ohhama I, Kumagai K, Ohno T, Tamura K, Tanida N, Sujishi M, Morisawa E, Fukuda Y, Okabayashi K, Kuroiwa T, Kano M (1977) Absorption of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) from the intestine (in Japanese). Jpn J Cancer Chemother 4: 347

    Google Scholar 

  28. Stewart CF, Arbuck SG, Fleming RA, Evans WE (1990) Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. J Clin Oncol 8: 1874

    Google Scholar 

  29. Suda Y, Uchida K, Okamura H, Oshima Y, Shimizu M, Miyakawa T, Okubo S, Shiina E, Hosoda Y, Tokura Y, Yamafuji K (1992) Blood concentrations of tegafur, uracil and 5-fluorouracil (5-FU) after UFT administration in the various reconstructions after gastrectomy (in Japanese with English abstract). Jpn J Cancer Chemother 19: 2181

    Google Scholar 

  30. Suga S, Kimura K, Yokoyama Y, Isobe K, Yoshida Y, Takada T, Sato A, Kuwabara T, Iwase H (1982) Studies on the designing of chemotherapy for gastric cancer in man, based on the tumor tissue concentration of anticancer agents. Gastroenterol Jpn 17: 295

    Google Scholar 

  31. Toide H, Akiyoshi H, Minato Y, Okuda H, Fujii S (1977) Comparative studies on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil. Jpn J Cancer Res 68: 553

    Google Scholar 

  32. Walther B, Clementsson C, Vallgren S, Ihse I, Akesson B (1989) Fat malabsorption in patients before and after total gastrectomy, studies by the triolein breath test. J Gastroenterol 24: 309

    Google Scholar 

  33. Yamamoto Y, Amano T, Fujimoto Y, Imada T, Tamura S, Noguchi Y, Matsumoto A (1987) The effect of gastrectomy on serum 5-FU concentrations of patients administered UFT per os (in Japanese with English abstract). Jpn J Cancer Clin 33: 377

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cancer Center of Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan

    Hideya Takeuchi, Ikuo Takahashi, Sadaaki Inutsuka, Hideo Baba, Shunji Kohnoe & Keizo Sugimachi

  2. Department of Surgery II, Faculty of Medicine, Kyushu University, 812, Fukuoka, Japan

    Yoshihiko Maehara, Tatsuo Oshiro & Keizo Sugimachi

Authors
  1. Yoshihiko Maehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideya Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatsuo Oshiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikuo Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sadaaki Inutsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideo Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shunji Kohnoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Keizo Sugimachi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maehara, Y., Takeuchi, H., Oshiro, T. et al. Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1∶4 tegafur and uracil combination. Cancer Chemother. Pharmacol. 33, 445–449 (1994). https://doi.org/10.1007/BF00686498

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686498

Keywords

Search

Navigation