Clinical pharmacokinetics of oseltamivir and its active metabolite oseltamivir carboxylate after oral administration in horses.

This research study explores how the drug oseltamivir, and its active element oseltamivir carboxylate, behaves in the bodies of horses, with specific focus on analyzing its absorption and elimination rates. Findings suggest that while a single dose provides a sufficient concentration to inhibit equine influenza viruses, the drug is rapidly eliminated and thus would require doses at intervals fewer than 10 hours for sustained efficacy.

Introduction to Oseltamivir

• Oseltamivir is the prodrug, or the biologically inactive compound, which can be metabolized in the body to produce the active drug, oseltamivir carboxylate (OC).
• OC is used in the treatment of influenza in several species, owing to its capability to inhibit these viruses.

Purpose of the Study

• The study was conducted to understand the clinical pharmacokinetics, which is how the body absorbs, distributes, metabolizes, and excretes the drug, of oseltamivir and its resultant active element, OC, in horses.
• Understanding this would allow for better administering strategies for OC in horses, to maximize its effectiveness while ensuring safety by reducing the risk of drug accumulation.

Findings of the Study

• The study found that OC barely binds to horse plasma proteins, with the rate being less than 1%. This is crucial because a lower plasma protein binding allows for more of the drug to be ‘free’, and therefore available to exert its pharmacological effects.
• A single dose of 2 mg/kg body weight of oseltamivir given orally to horses results in sufficient plasma concentration of OC to inhibit equine influenza A viruses.
• However, OC is also rapidly eliminated from the body. The time taken for the amount of drug in the body to reduce by half, also known as the elimination half-life, is just 2.5 hours.
• This indicates that if the drug is administered just once, suitable concentrations would only be retained for less than 10 hours, so increased frequency of dosing would be needed for sustained efficacy.

Implications of the Study

• The findings of this study have implications for both the treatment of influenza in horses, and investigations of the pharmacokinetics of OC in other species and contexts.
• They can be used to adjust dosing regimens to ensure that the necessary therapeutic concentration in the plasma is maintained over time, which could improve the effectiveness of ongoing treatment for influenza in horses.