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Titolo:
Pharmacodynamic evaluation of RWJ-270201, a novel neuraminidase inhibitor,in a lethal murine model of influenza predicts efficacy for once-daily dosing
Autore:
Drusano, GL; Preston, SL; Smee, D; Bush, K; Bailey, K; Sidwell, RW;
Indirizzi:
Albany Med Coll, Clin Res Inst, Div Clin Pharmacol, Albany, NY 12208 USA Albany Med Coll Albany NY USA 12208 Clin Pharmacol, Albany, NY 12208 USA Utah State Univ, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322Utah State Univ, Logan, UT 84322 USA RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA RW Johnson Pharmaceut Res Inst Raritan NJ USA 08869 Raritan, NJ 08869 USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 7, volume: 45, anno: 2001,
pagine: 2115 - 2118
SICI:
0066-4804(200107)45:7<2115:PEORAN>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
9
Recensione:
Indirizzi per estratti:
Indirizzo: Drusano, GL Albany Med Coll, Clin Res Inst, Div Clin Pharmacol, Albany, NY12208 USA Albany Med Coll Albany NY USA 12208 col, Albany, NY 12208 USA
Citazione:
G.L. Drusano et al., "Pharmacodynamic evaluation of RWJ-270201, a novel neuraminidase inhibitor,in a lethal murine model of influenza predicts efficacy for once-daily dosing", ANTIM AG CH, 45(7), 2001, pp. 2115-2118

Abstract

We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus A/Shong- dong/09/93 (H3N2). Treatment was administered by gavage. Five doses (1 to 10 mg/kg of body weight) and three schedules (every 24, 12, and 8 h) were evaluated with 10 mice per group. There were 39 placebo-treated mice. Drug exposure was evaluated for infected mice. Exposures were calculated after population modeling of all the plasma concentration-time data simulataneously using the NPEM3 program. Evaluation of dose and schedule with Kaplan-Meier analysis and Cox proportional hazards modeling demonstrated that schedule offered no explanatorypower relative to dose alone. Evaluation of peak concentration, trough concentration, and area under the concentration-time curve (AUC) by the same methods revealed that AUC was the dynamically linked variable. Again, schedule offered no further explanatory power when included in the model with AUG. This indicates that AUC is the linked variable and that the anti-influenza effect of RWJ-270201 is independent of schedule. We conclude that once-daily dosing of RWJ-270201 should be evaluated in clinical trials of influenza therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 14:57:02