title: Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese volunteers.
abstract: The 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.
  
  
  
  The 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.
  
  
  
  The 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.
  
  
  
  The results confirmed that a dose adjustment for oseltamivir in obese individuals is not necessary on the basis of its pharmacokinetics.
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Kalayanee
authors.initials: K
authors.lastname: Chairat
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Podjanee
authors.initials: P
authors.lastname: Jittamala
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Warunee
authors.initials: W
authors.lastname: Hanpithakpong
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Sasithon
authors.initials: S
authors.lastname: Pukrittayakamee
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Joel
authors.initials: J
authors.lastname: Tarning
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism*; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D014838:Volunteers; D055815:Young Adult
chemical_list: D053139:Oseltamivir; C535162:oseltamivir carboxylate
keywords: influenza; obesity; oseltamivir; population pharmacokinetics
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