Oral oseltamivir in human experimental influenza B infection.
Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.
Hayden
F G
FG
University of Virginia School of Medicine, Department of Internal Medicine, Charlottesville, USA. fgh@virginia.edu
Jennings
L
L
Robson
R
R
Schiff
G
G
Jackson
H
H
Rana
B
B
McClelland
G
G
Ipe
D
D
Roberts
N
N
Ward
P
P
D000081:Acetamides / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D009981:Influenza B virus / Q000302:isolation & purification / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D008875:Middle Aged; D053139:Oseltamivir
D000081:Acetamides; D000998:Antiviral Agents; D053139:Oseltamivir