Abstract
AimsThe aims of the present study were to compare the pharmacokinetics of oseltamivir and its active antiviral metabolite oseltamivir carboxylate in obese and non‐obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and oseltamivir carboxylate.MethodsThe population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese [body mass index (BMI) ≥30 kg m−2) and 12 non‐obese (BMI <30 kg m−2) Thai adult volunteers receiving a standard dose of 75 mg and a double dose of 150 mg in a randomized sequence. Concentration–time data were collected and analysed using nonlinear mixed‐effects modelling.ResultsThe pharmacokinetics of oseltamivir and oseltamivir carboxylate were described simultaneously by first‐order absorption, with a one‐compartment disposition model for oseltamivir, followed by a metabolism compartment and a one‐compartment disposition model for oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance {3.84% increase for each 10 ml min−1 increase in creatinine clearance [95% confidence interval (CI) 0.178%, 8.02%]}. Obese individuals had an approximately 25% (95% CI 24%, 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI 19%, 23%) and 10% higher oseltamivir carboxylate clearance (95% CI 9%, 11%) compared with non‐obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate.ConclusionsThe results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics.
Highlights
A novel influenza virus, A(H1N1)pdm09, apparently of swine origin, emerged in March 2009 in North America and spread rapidly among humans around the world
10% higher oseltamivir carboxylate clearance compared with non-obese individuals
Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance
Summary
A novel influenza virus, A(H1N1)pdm, apparently of swine origin, emerged in March 2009 in North America and spread rapidly among humans around the world. The World Health Organization (WHO) declared the end of the pandemic in August 2010, A(H1N1)pdm continues to cause illness as a seasonal influenza virus. Poor clinical outcomes were observed in several patient populations infected with this virus – mainly geriatric patients aged ≥65 years, pregnant patients in the third trimester, obese patients and patients with concomitant chronic illnesses [1]. Higher doses of oseltamivir and longer durations of treatment were recommended for the treatment of A(H1N1)pdm influenza-infected patients with severe or progressive clinical presentations [2]. Previous studies suggested that a higher dose (i.e. 150 mg oseltamivir) provided no additional clinical benefit over the standard dose in patients with severe influenza [3,4,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
