Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
5-ETHYNYLURACIL (776C85) - EFFECTS ON THE ANTITUMOR-ACTIVITY AND PHARMACOKINETICS OF TEGAFUR, A PRODRUG OF 5-FLUOROURACIL
Autore:
CAO S; BACCANARI DP; JOYNER SS; DAVIS ST; RUSTUM YM; SPECTOR T;
Indirizzi:
GLAXO WELLCOME RES & DEV,5 MOORE DR RES TRIANGLE PK NC 27709 GLAXO WELLCOME RES & DEV RES TRIANGLE PK NC 27709 ROSWELL PK CANC INST,GRACE CANC DRUG CTR BUFFALO NY 14263
Titolo Testata:
Cancer research
fascicolo: 24, volume: 55, anno: 1995,
pagine: 6227 - 6230
SICI:
0008-5472(1995)55:24<6227:5(-EOT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY; CANCER-PATIENTS; FTORAFUR; URACIL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
S. Cao et al., "5-ETHYNYLURACIL (776C85) - EFFECTS ON THE ANTITUMOR-ACTIVITY AND PHARMACOKINETICS OF TEGAFUR, A PRODRUG OF 5-FLUOROURACIL", Cancer research, 55(24), 1995, pp. 6227-6230

Abstract

We studied the effects of 5-ethynyluracil (776C85 and 776C), a potentmechanism-based inactivator of dihydropyrimidine dehydrogenase, on the antitumor efficacy and pharmacokinetics of tegafur (FT), a prodrug of 5-fluorouracil (5-FU), in rats with large s.c. colon carcinoma, Ratswere dosed p.o. once daily for 7 days with either FT, FT and uracil in a 1:4 molar ratio (UFT), FT 1 h after 776C (776C/PT), or UFT 1 h after 776C (776C/UFT), 776C, which was dosed at 1 mg/kg, had neither intrinsic antitumor activity nor toxicity, The rank order in antitumor efficacy at the maximal tolerated dose of the FT (mg/kg/day) component was 776C/FT (5 mg/kg/day) greater than or equal to UFT (80 mg/kg/day) = 776C/UFT (5 mg/kg/ day) much greater than FT (200 mg/kg/day). One-hundred % of rats treated with 776C/FT had complete and sustained tumor regression with no severe toxicity. The area under the plasma 5-FU concentration versus the time curve generated from UFT, FT, and 776C/FT at their maximum tolerated dose was 140, 50, and 27 mu M . h, respectively. The area under the concentration in plasma versus time curve did not correlate with the rank order of antitumor efficacy, The vast majority of 5-FU derived from FT (alone) appeared to be rapidly catabolized,Furthermore, plasma exposure of 5-FU derived from UFT was more variable than that from 776C/FT. Each therapy also produced different levelsof plasma uracil, Endogenous plasma uracil levels (1-3 mu M) were notaffected by FT but increased to 100 mu M after dosing with 776C, Plasma uracil from UFT was 800 mu M 1 h after dosing, These results suggest that moderately elevated uracil (776C/FT) may be beneficial, whereasuracil that is greatly elevated during the first 5 h (UFT) and 5-FU catabolites (FT alone) may interfere with antitumor efficacy, 776C, coadministered with FT, could provide once-a-day oral therapy for cancer patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 14:58:28