tetano
Editor, Senior Moderator
Br J Clin Pharmacol. 2016 Jan 26. doi: 10.1111/bcp.12892. [Epub ahead of print]
[h=1]Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and Non-obese volunteers.[/h] Chairat K[SUP]1[/SUP], Jittamala P[SUP]1,[/SUP][SUP]2[/SUP], Hanpithakpong W[SUP]1[/SUP], Day NP[SUP]1,[/SUP][SUP]3[/SUP], White NJ[SUP]1,[/SUP][SUP]3[/SUP], Pukrittayakamee S[SUP]2[/SUP], Tarning J[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] 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.
[h=4]METHODS:[/h] The population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese (body mass index; BMI ≥30 kg/m[SUP]2[/SUP] ) and 12 non-obese (BMI <30 kg/m[SUP]2[/SUP] ) 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] This confirmed that dose adjustment of oseltamivir in obese individuals was not necessary on a pharmacokinetic basis.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] influenza; obesity; oseltamivir; population pharmacokinetics
PMID: 26810861 [PubMed - as supplied by publisher]
[h=1]Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and Non-obese volunteers.[/h] Chairat K[SUP]1[/SUP], Jittamala P[SUP]1,[/SUP][SUP]2[/SUP], Hanpithakpong W[SUP]1[/SUP], Day NP[SUP]1,[/SUP][SUP]3[/SUP], White NJ[SUP]1,[/SUP][SUP]3[/SUP], Pukrittayakamee S[SUP]2[/SUP], Tarning J[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]AIMS:[/h] 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.
[h=4]METHODS:[/h] The population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate were evaluated in 12 obese (body mass index; BMI ≥30 kg/m[SUP]2[/SUP] ) and 12 non-obese (BMI <30 kg/m[SUP]2[/SUP] ) 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.
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] This confirmed that dose adjustment of oseltamivir in obese individuals was not necessary on a pharmacokinetic basis.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] influenza; obesity; oseltamivir; population pharmacokinetics
PMID: 26810861 [PubMed - as supplied by publisher]