DDMODEL00000307: Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese volunteers

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Short description:
Population pharmacokinetic properties of oseltamivir and oseltamivir carboxylate in healthy in obese and non-obese individuals
Original code
  • Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese volunteers.
  • Chairat K, Jittamala P, Hanpithakpong W, Day NP, White NJ, Pukrittayakamee S, Tarning J
  • British journal of clinical pharmacology, 6/2016, Volume 81, Issue 6, pages: 1103-1112
  • Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • 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.
Joel Tarning
Context of model development: Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese); Variability sources in PK and PD (CYP, Renal, Biomarkers);
Long technical model description: A detailed explanation of the model can be found in the published manuscript, Population pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese volunteers (published in British Journal of Clinical Pharmacology);
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: There is an increased risk of poor outcome observed in obese patients infected with A(H1N1) pdm09 influenza. Previous reports found that obese patients have a lower overall exposure to oseltamivir but a similar exposure to the active metabolite, oseltamivir carboxylate. However, the effect of obesity has previously only been characterized in severely obese volunteers and not in a study including both obese and non-obese control subjects. The aims of this study were to compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in obese and non-obese individuals.;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Anti-infectives;
Annotations are correct.
This model is not certified.
  • Model owner: Joel Tarning
  • Submitted: Oct 3, 2019 7:38:35 AM
  • Last Modified: Oct 3, 2019 7:38:35 AM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Oct 3, 2019 7:38:35 AM
    • Submitted by: Joel Tarning
    • With comment: Updated model annotations.
 
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