Oseltamivir.

Abstract

Oseltamivir is the oral prodrug of GS4071, a selective inhibitor of influenza A and B viral neuraminidase. After absorption from the gastrointestinal tract oseltamivir is efficiently converted to GS4071, which is maintained at high and sustained concentrations in plasma. Based on studies in rats and ferrets, GS4071 appears to be effectively distributed to all tissues, including major sites of infection in the upper and lower respiratory tracts. Oral oseltamivir was an effective treatment in naturally occurring influenza when administered within 36 hours of symptom onset, reducing both the duration and severity of symptoms and the incidence of secondary complications in influenza-infected patients enrolled in 2 large placebo-controlled, double-blind trials. Prophylactic oral administration of oseltamivir was effective in reducing the incidence of influenza illness according to pooled data from 2 large placebo-controlled, double-blind trials of healthy nonimmunised volunteers during periods of seasonal influenza activity. The reported incidence of viral resistance to GS4071 was low in clinical isolates from oseltamivir treatment studies. All known GS4071 resistant genotypes are growth disadvantaged and display significantly reduced infectivity in animals. Oseltamivir was well tolerated in human volunteers and patients in clinical trials. Treatment-related adverse events (primarily gastrointestinal) were mild and transient in nature.