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Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and Non-obese volunteers.

Abstract:
The aims of this study were to compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese individuals and to determine the effect of obesity on the pharmacokinetic properties of oseltamivir and the active antiviral metabolite 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 randomised sequence. Concentration-time data were collected and analysed with nonlinear mixed-effects modelling.The pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, were described simultaneously by first-order absorption, with a one-compartment disposition model for oseltamivir followed by a metabolism compartment and one-compartment disposition of oseltamivir carboxylate. Creatinine clearance was a significant predictor of oseltamivir carboxylate clearance (3.84% increase for each 10 mL/min increase of creatinine clearance, 95% confidence interval [95% CI] of 0.178 to 8.02%). Obese individuals had an approximately 25% (95% CI of 24% to 28%) higher oseltamivir clearance, 20% higher oseltamivir volume of distribution (95% CI of 19% to 23%) and 10% higher oseltamivir carboxylate clearance (95% CI of 9% to 11%) compared to non-obese individuals. However, these altered pharmacokinetic properties were small and did not change the overall exposure to oseltamivir carboxylate.This confirmed that dose adjustment of oseltamivir in obese individuals was not necessary on a pharmacokinetic basis.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1111/bcp.12892

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Tropical Medicine
Role:
Author


Publisher:
Wiley
Journal:
British Journal of Clinical Pharmacology More from this journal
Volume:
81
Issue:
6
Pages:
1103–1112
Publication date:
2016-01-26
DOI:
EISSN:
1365-2125
ISSN:
0306-5251


Language:
English
Keywords:
Pubs id:
pubs:597953
UUID:
uuid:57e4ad82-cbe5-4cd7-83e1-2d2cb77bb265
Local pid:
pubs:597953
Source identifiers:
597953
Deposit date:
2016-01-29

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