Pharmacokinetic study of S-1
| Autor: | Max E. Scheulen, Dirk Strumberg, Paul Scigalla, Kredtke S, Mende B, Urrea Pd, Ralf A. Hilger, Makris L, Axel-Rainer Hanauske, Jürgen Krauss, Thyssen D |
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| Rok vydání: | 2009 |
| Předmět: |
Antimetabolites
Antineoplastic Pyrimidine Pyridines Administration Oral Biological Availability Pharmacology Tegafur 2-Pyridinylmethylsulfinylbenzimidazoles chemistry.chemical_compound Pharmacokinetics medicine Dihydropyrimidine dehydrogenase Humans Pharmacology (medical) Uracil Pantoprazole Dihydrouracil Dehydrogenase (NADP) Gastrointestinal tract Clinical Trials as Topic Triazines Fasting Gastric Acidity Determination Prodrug Hydrogen-Ion Concentration Anti-Ulcer Agents In vitro Drug Combinations Oxonic Acid chemistry Food Area Under Curve beta-Alanine Fluorouracil medicine.drug Half-Life |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 47(1) |
| ISSN: | 0946-1965 |
| Popis: | Since the first synthesis of 5-FU in 1957 fluoropyrimidines have been widely used clinically in the treatment of solid tumors. Because of good anti-tumor efficacy of 5-FU as a single agent on gastrointestinal tract tumors, many attempts have been made to develop new and superior 5-FU derivatives. Recently, S-1, a new antitumor medication based on the biochemical modulation of 5-FU, (1 M Tegafur (ftorafur, FT), 0.4 M 5-chloro-2, 4-dihydroxypyridine (gimeracil, CDHP), and 1 M potassium oxonate (oteracil, Oxo)) was developed. FT, which is a prodrug of 5-FU, plays a role as an effector. Both CDHP and Oxo, which do not have antitumor activity themselves act as modulators. CDHPcompetitively inhibits dihydropyrimidine dehydrogenase (DPD, EC 1.3.1.2), which in vitro degrades 5-FU about 180 times more effectively than uracil, leading to prolonged concentrations of 5-FU in blood. Oxo competitively inhibits pyrimidine phosphoribosyl transferase (EC 2.4.2.10), which converts 5-FU to 5fluorouridine 5’-monophosphate. Oxo is distributed primarily to the gastrointestinal tract after p.o. administration. This component of S-1 decreases the incorporation of 5-fluorouridine triphosphate into RNA in the gastrointestinal mucosa and reduces the incidence of diarrhea. |
| Databáze: | OpenAIRE |
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