Oseltamivir: a clinical and pharmacological perspective

Abstract

Oseltamivir 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.

Probable Tiger-to-Tiger Transmission of Avian Influenza H5N1

“…In vitro studies have demonstrated the potent antiviral activity of oseltamivir against all strains of influenza A tested, including the avian H5N1 virus recently implicated in human influenza cases in Hong Kong (11). In this study, the failure of treatment might have been attributable to various factors such as dosage, pharmacokinetics, or host metabolism, since no changes were seen in the neuraminidase.…”

Molecular photoswitches in aqueous environments

“… 555 However, charged moieties can also hinder the internalization pathway by diffusion through the lipid bilayer due to insufficient lipophilicity of the compound. 556 These contradicting effects, improved adherence and decreased diffusion through the membrane, illustrate the importance of a balanced design of drug-like molecules.…”

Correlation of days of illness on which oseltamivir was started with outcome in swine flu patients, in Government Medical College, Aurangabad (Jan-2015 to May 2015)

“…The terminal plasma elimination half-life is 1.8 hours in healthy adults. 12 It is reported that survival is significantly increased by timely oseltamivir in serious cases. It is generally well tolerated except for few cases who get nausea, 13 vomiting and diarrhoea.…”