5-Ethynyluracil (776C85): A Potent Modulator of the Pharmacokinetics and Antitumor Efficacy of 5-Fluorouracil
5-Ethynyluracil (5-EU, 776C85) is a mechanism-based irreversible inhibitor of dihydropyrimidine dehydrogenase (EC 1.3.1.2), the rate-determining enzyme in 5-fluorouracil (5-FU) catabolism. In the present study, 5-EU was found to be a potent modulator of 5-FU catabolism in mice and rats. Liver extracts prepared up to 6 hr after a 5-EU dose (2 mg/kg) were >96% inhibited in their ability to catalyze 5-FU degradation. 5-EU treatment increased the elimination t1/2and the area under the plasma concentration-time curve of 5-FU. 5-FU oral bioavailability was ≈100% in rats pretreated with 5-EU. Consequently, 5-EU induced a linear relationship between the area under the plasma concentration-time curve and the oral dose of 5-FU. As expected from the preservation of plasma 5-FU, 5-EU potentiated the antitumor activity and the toxicity of 5-FU in two mouse tumor models (Colon 38 and MOPC-315). However, 5-EU potentiated the antitumor activity to a greater degree and thereby increased the therapeutic index of 5-FU 2- to 4-fold..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
1993 |
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| Erschienen: |
1993 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:90 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baccanari, David P. [VerfasserIn] |
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| Links: |
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| Themen: |
Biochemical Modulation |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
JST07007643X |
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| 100 | 1 | |a Baccanari, David P. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 5-Ethynyluracil (776C85): A Potent Modulator of the Pharmacokinetics and Antitumor Efficacy of 5-Fluorouracil |
| 264 | 1 | |c 1993 | |
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| 337 | |a Computermedien |b c |2 rdamedia | ||
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| 520 | |a 5-Ethynyluracil (5-EU, 776C85) is a mechanism-based irreversible inhibitor of dihydropyrimidine dehydrogenase (EC 1.3.1.2), the rate-determining enzyme in 5-fluorouracil (5-FU) catabolism. In the present study, 5-EU was found to be a potent modulator of 5-FU catabolism in mice and rats. Liver extracts prepared up to 6 hr after a 5-EU dose (2 mg/kg) were >96% inhibited in their ability to catalyze 5-FU degradation. 5-EU treatment increased the elimination t1/2and the area under the plasma concentration-time curve of 5-FU. 5-FU oral bioavailability was ≈100% in rats pretreated with 5-EU. Consequently, 5-EU induced a linear relationship between the area under the plasma concentration-time curve and the oral dose of 5-FU. As expected from the preservation of plasma 5-FU, 5-EU potentiated the antitumor activity and the toxicity of 5-FU in two mouse tumor models (Colon 38 and MOPC-315). However, 5-EU potentiated the antitumor activity to a greater degree and thereby increased the therapeutic index of 5-FU 2- to 4-fold. | ||
| 540 | |a Copyright 1993 The National Academy of Sciences of the United States of America | ||
| 650 | 4 | |a Medical Sciences | |
| 650 | 4 | |a Biochemical Modulation | |
| 650 | 4 | |a Therapeutic Index | |
| 650 | 4 | |a Potentiation | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Pharmacology |x Clinical pharmacology |x Pharmacokinetics |x Dosage | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Tumors | |
| 650 | 4 | |a Health sciences |x Medical treatment | |
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x Body composition |x Body fluids |x Blood |x Blood plasma | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Pharmacology |x Clinical pharmacology |x Pharmacokinetics | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Pharmacology |x Clinical pharmacology |x Pharmacokinetics |x Bioavailability | |
| 650 | 4 | |a Physical sciences |x Chemistry |x Chemical compounds |x Chemicals |x Polymers |x Biopolymers |x Proteins |x Enzymes | |
| 650 | 4 | |a Health sciences |x Health care industry |x Health care administration | |
| 650 | 4 | |a Biological sciences |x Biology |x Anatomy |x Excretory system |x Excreta |x Urine | |
| 650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Rodents |x Mice | |
| 655 | 4 | |a research-article | |
| 700 | 1 | |a Davis, Stephen T. |e verfasserin |4 aut | |
| 700 | 1 | |a Knick, Vincent C. |e verfasserin |4 aut | |
| 700 | 1 | |a Spector, Thomas |e verfasserin |4 aut | |
| 773 | 1 | 8 | |g volume:90 |g year:1993 |g number:23 |g pages:11064-11068 |
| 856 | 4 | 0 | |u https://www.jstor.org/stable/2363649 |3 Volltext |
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| 952 | |d 90 |j 1993 |e 23 |h 11064-11068 | ||