OBJECTIVE:Oseltamivir is the only oral neuraminidase inhibitor currently available; we determined the tolerability and antiviral efficacy of oral peramivir for treatment and prophylaxis of experimental human influenza A and B. PARTICIPANTS: 288 susceptible, healthy volunteers (ages 18-45) were inoculated intranasally with A/Texas/36/ 91/H1N1 or B/Yamagata/16/88 virus in four randomized, double-blind, placebo-controlled trials. INTERVENTIONS: For treatment dosing was initiated at 24 h after inoculation with peramivir doses ranging from 100-800 mg/day for 5 days. For prophylaxis dosing was initiated 24 h before inoculation and continued for 4 days with peramivir doses ranging from 50-800 mg/day. OUTCOMES: The primary outcome measure for treatment was quantitative viral detection defined by the area under the curve (AUC) for nasal wash viral titres. For prophylaxis the primary outcome measure was the incidence of virus recovery. RESULTS: In influenza A treatment, peramivir 400 mg q24h and 200mg q12h, but not lower doses, resulted in significant reductions in viral titre AUC. In influenza B treatment, both 400 and 800/400 mg once daily dose groups reduced AUC values. In influenza A prophylaxis, the percentage of individuals with nasal viral shedding did not differ significantly in the placebo (58%), 50 mg (61%), 200 mg (37%) and 400 mg (31%) dose groups. In influenza B prophylaxis, shedding frequencies were similar in placebo (55%), 200 mg (41%), 400 mg (35%) and 800 mg (47%) dose groups. The drug was well tolerated in all four studies, with nausea and headache being the most common side effects. No drug-resistant variants were detected. CONCLUSION: Early treatment with peramivir was associated with significant antiviral effects in experimentally induced influenza in humans. Prophylaxis did not significantly reduce viral shedding. The relatively low blood peramivir concentrations observed may explain the lack of more robust antiviral effects, and parenteral dosing should be studied.
RCT Entities:
OBJECTIVE:Oseltamivir is the only oral neuraminidase inhibitor currently available; we determined the tolerability and antiviral efficacy of oral peramivir for treatment and prophylaxis of experimental human influenza A and B. PARTICIPANTS: 288 susceptible, healthy volunteers (ages 18-45) were inoculated intranasally with A/Texas/36/ 91/H1N1 or B/Yamagata/16/88 virus in four randomized, double-blind, placebo-controlled trials. INTERVENTIONS: For treatment dosing was initiated at 24 h after inoculation with peramivir doses ranging from 100-800 mg/day for 5 days. For prophylaxis dosing was initiated 24 h before inoculation and continued for 4 days with peramivir doses ranging from 50-800 mg/day. OUTCOMES: The primary outcome measure for treatment was quantitative viral detection defined by the area under the curve (AUC) for nasal wash viral titres. For prophylaxis the primary outcome measure was the incidence of virus recovery. RESULTS: In influenza A treatment, peramivir 400 mg q24h and 200mg q12h, but not lower doses, resulted in significant reductions in viral titre AUC. In influenza B treatment, both 400 and 800/400 mg once daily dose groups reduced AUC values. In influenza A prophylaxis, the percentage of individuals with nasal viral shedding did not differ significantly in the placebo (58%), 50 mg (61%), 200 mg (37%) and 400 mg (31%) dose groups. In influenza B prophylaxis, shedding frequencies were similar in placebo (55%), 200 mg (41%), 400 mg (35%) and 800 mg (47%) dose groups. The drug was well tolerated in all four studies, with nausea and headache being the most common side effects. No drug-resistant variants were detected. CONCLUSION: Early treatment with peramivir was associated with significant antiviral effects in experimentally induced influenza in humans. Prophylaxis did not significantly reduce viral shedding. The relatively low blood peramivir concentrations observed may explain the lack of more robust antiviral effects, and parenteral dosing should be studied.
Authors: Matthew J Memoli; Lindsay Czajkowski; Susan Reed; Rani Athota; Tyler Bristol; Kathleen Proudfoot; Sarah Fargis; Matthew Stein; Rebecca L Dunfee; Pamela A Shaw; Richard T Davey; Jeffery K Taubenberger Journal: Clin Infect Dis Date: 2014-11-20 Impact factor: 9.079
Authors: E Bart Tarbet; Masako Maekawa; Yousuke Furuta; Y S Babu; John D Morrey; Donald F Smee Journal: Antiviral Res Date: 2012-03-10 Impact factor: 5.970
Authors: Jacqueline M McBride; Jeremy J Lim; Tracy Burgess; Rong Deng; Michael A Derby; Mauricio Maia; Priscilla Horn; Omer Siddiqui; Daniel Sheinson; Haiyin Chen-Harris; Elizabeth M Newton; Dimitri Fillos; Denise Nazzal; Carrie M Rosenberger; Maikke B Ohlson; Rob Lambkin-Williams; Hosnieh Fathi; Jeffrey M Harris; Jorge A Tavel Journal: Antimicrob Agents Chemother Date: 2017-10-24 Impact factor: 5.191
Authors: Jacqueline M McBride; Jeremy J Lim; Tracy Burgess; Rong Deng; Michael A Derby; Mauricio Maia; Priscilla Horn; Omer Siddiqui; Daniel Sheinson; Haiyin Chen-Harris; Elizabeth M Newton; Dimitri Fillos; Denise Nazzal; Carrie M Rosenberger; Maikke B Ohlson; Rob Lambkin-Williams; Hosnieh Fathi; Jeffrey M Harris; Jorge A Tavel Journal: Antimicrob Agents Chemother Date: 2017-12-21 Impact factor: 5.191
Authors: David A Boltz; Natalia A Ilyushina; C Shane Arnold; Y Sudhakar Babu; Robert G Webster; Elena A Govorkova Journal: Antiviral Res Date: 2008-06-23 Impact factor: 5.970
Authors: Nadezhda E Yun; Nathaniel S Linde; Michele A Zacks; Ian G Barr; Aeron C Hurt; Jeanon N Smith; Natallia Dziuba; Michael R Holbrook; Lifang Zhang; John M Kilpatrick; C Shane Arnold; Slobodan Paessler Journal: Virology Date: 2008-01-29 Impact factor: 3.616