• K E Doucette and F Y Aoki.
• Section of Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada. nelsonak@ms.umanitoba.ca
• Expert Opin Pharmacother. 2001 Oct 1; 2 (10): 1671-83.

AbstractOseltamivir is the ethyl ester prodrug of the antiviral molecule, oseltamivir carboxylate, a potent and selective inhibitor of influenza A and B neuraminidase (NA) (sialidase). It is highly bioavailable in capsule and suspension formulations and, after conversion to the active metabolite in the liver, distributes throughout the body, including the upper and lower respiratory tract. Oseltamivir carboxylate is 3% bound to human plasma proteins and eliminated through the kidneys by a first-order process as unchanged drug by glomerular filtration and tubular secretion by an anionic transporter system. Given these characteristics, its potential for adverse interactions with other drugs appears limited to those arising from competitive inhibition of excretion by the renal tubular epithelial cell anionic transporter. The terminal plasma elimination half-life is 1.8 h in healthy adults. Renal clearance is inversely related to renal function and averages 23 h after oral administration in individuals with creatinine clearance < 30 ml/min. In vitro studies have demonstrated potent antiviral activity against all strains of influenza A and B tested including avian H5N1 and H9N2 strains recently implicated in human cases in Hong Kong. Studies of both experimental and naturally-occurring influenza in humans have demonstrated efficacy in both the prevention and treatment of influenza A and B infection. The drug is well-tolerated with the only clinically important side effect being mild gastrointestinal upset. Resistance has been uncommonly seen after clinical use; the highest incidence was 5.5% in children treated for influenza A infection for 5 days. Viruses that develop resistance appear to be less virulent in laboratory animals and to replicate less efficiently than parent strains. Although oseltamivir and the M2 ion channel inhibitors, amantadine and rimantadine, have not been directly compared in clinical trials, the greater breadth of spectrum of oseltamivir, its modest side effect profile compared to amantadine and its lesser propensity to engender the emergence of transmissible drug-resistant strains all suggest strongly that oseltamivir is a significant new agent for the prevention and treatment of influenza. A series of controlled trials comparing M2 ion channel inhibitor drugs and the new neuraminidase (NA) inhibitor agents are now needed to test this hypothesis and thereby to further advance the science of antiviral drug use to control influenza.

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