Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations

Abstract

Influenza is a transmissible viral pathogen that continues to cause substantial morbidity and mortality. Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication. Treatment of infected children ≥1 year and adults of all ages may decrease the severity and duration of the symptoms of infection, while prophylactic dosing can prevent their onset. Oseltamivir is ingested in the form of a prodrug (oseltamivir phosphate) that is rapidly converted by hepatic esterases into the active metabolite, oseltamivir carboxylate. Oseltamivir carboxylate has high bioavailability and penetrates sites of infection at concentrations that are sufficient to inhibit viral replication. The pharmacokinetics of oseltamivir and oseltamivir carboxylate are dose proportional after repeated doses of up to 500 mg twice daily. This predictable profile means that oseltamivir is suitable for use in diverse patient populations, which may include young children and elderly patients, various ethnic groups and those with renal or hepatic impairment. As the potential for drug interactions is low, oseltamivir is also suitable for use in patients with co-morbid conditions who are likely to be receiving concomitant medications.

Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight Is Not Necessary

“…Ariano and colleagues recently demonstrated that the pharmacokinetics of oseltamivir carboxylate are not reduced in critically ill patients across a weight range of approximately 50 to 200 kg (2). The median (interquartile range [IQR]) AUC 0-ϱ in critically ill patients with normal kidney function was 4,854 (3,109, 10,820) ng ⅐ h/ml (2), compared to a median (IQR) AUC 0-ϱ of 4022 (3,481,4,747) ng ⅐ h/ml in the current study (noncompartmental estimate). Similar to our findings, Ariano and colleagues also demonstrated that pharmacokinetic parameters of oseltamivir carboxylate are not influenced by body weight (2).…”

“…Oseltamivir carboxylate is a small molecule (284.4 g/mol) that is virtually unbound to plasma proteins (3% protein binding) (4). Thus, lung exposures may be inferred from oseltamivir carboxylate plasma concentration-time data.…”

Species-Dependent Uptake of Glycylsarcosine but Not Oseltamivir in Pichia pastoris Expressing the Rat, Mouse, and Human Intestinal Peptide Transporter PEPT1

“…Oseltamivir phosphate (Tamiflu), an ethyl ester prodrug of the active metabolite Ro 64-0802 (oseltamivir carboxylate), is used for the treatment and prophylaxis of influenza A or B in adults and children Ն1 year of age (Moscona, 2005;Davies 2010). The prodrug is well absorbed (75-80%) from the gastrointestinal tract and is efficiently converted by human liver carboxylesterase 1 to Ro 64-0802 (Shi et al, 2006).…”

Development and evaluation of a dry powder formulation of liposome-encapsulated oseltamivir phosphate for inhalation

“…Oseltamivir phosphate (OP) was recommended by the World Health Organization (WHO) for both treatment and prophylaxis of influenza. As an important firstline defense in the event of a flu pandemic, it has been licensed to Hoffmann-La Roche Ltd. under the trade name Tamiflu Õ (Davies, 2010). As a pro-drug, OP can be readily absorbed from the gastrointestinal tract whose absolute bioavailability is about 75-80% and extensively converted by hepatic carboxylesterases to the active metabolite oseltamivir carboxylate (OSCA), a potent and selective inhibitor of influenza virus neuraminidase (Heinig & Bucheli, 2008;Dutkowski et al, 2010) that is essential for the release of progeny influenza viruses from infected host cells, which in turn prevents infection of new host cells and viral spread throughout the respiratory tract (Ghosh et al, 2010).…”