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Titolo:
In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RWJ-270201
Autore:
Sidwell, RW; Smee, DF; Huffman, JH; Barnard, DL; Bailey, KW; Morrey, JD; Babu, YS;
Indirizzi:
Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 nst Antiviral Res, Logan, UT 84322 USA BioCryst Pharmaceut Inc, Birmingham, AL 35244 USA BioCryst Pharmaceut IncBirmingham AL USA 35244 Birmingham, AL 35244 USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 3, volume: 45, anno: 2001,
pagine: 749 - 757
SICI:
0066-4804(200103)45:3<749:IVIVEO>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
RANDOMIZED CONTROLLED TRIAL; EFFICACY; SAFETY; OSELTAMIVIR; INFECTIONS; ZANAMIVIR; MICE; PRODRUG; PREVENTION; GS-4071;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Sidwell, RW Utah State Univ, Inst Antiviral Res, 5600 Old Main Hill, Logan, UT 84322 USA Utah State Univ 5600 Old Main Hill Logan UT USA 84322 4322 USA
Citazione:
R.W. Sidwell et al., "In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RWJ-270201", ANTIM AG CH, 45(3), 2001, pp. 749-757

Abstract

The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatmentwas by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure, The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day, Oseltamivir was generally up to 10-fold less effective than RWJ-270201, Ribavirin was also inhibitory but was less tolerated by the mire at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers, RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201exhibiting the greater inhibitory effect, a titer reduction of > 10(4) cell culture 50% infective doses (CCID50)/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 10(1.2) CCID50/g, whereas titers from oseltamivir-treated animals were > 10(3) CCID50/g, Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8, Bothneuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day, These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:56:03