Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects
One in three Americans are obese. Obese subjects may or may not need higher doses of the anti-flu drug known as Tamiflu (oseltamivir). The current study is being done to see if the t FDA approved dose of oseltamivir will achieve similar concentrations in obese healthy volunteers compared that previously shown in non-obese volunteers.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
- Plasma Pharmacokinetics [ Time Frame: 6 months ] [ Designated as safety issue: No ]To characterize the single-dose plasma pharmacokinetics of oseltamivir carboxylate administered by mouth in obese subjects.
- Comparison of pharmacokinetic data in obese subjects to historical data [ Time Frame: 6 months ] [ Designated as safety issue: No ]To compare the single and multiple-dose plasma pharmacokinetics of oseltamivir carboxylate administered by mouth in obese subjects to normal weight subjects
|Study Start Date:||July 2010|
|Study Completion Date:||December 2010|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
The incidence of obesity has increased dramatically over the past two decades in the United States (US). Twenty-five percent of adult Americans are now classified as obese. Obesity is associated with physiological alterations that can affect drug clearance and volume of distribution. Obese subjects are often excluded from phase 1 pharmacokinetic studies. As a result, drug dosing regimens developed for clinical use may not be appropriate for the obese population. Use of fixed dosing regimens may result in under dosing of obese patients. In contrast adjustment of drug dosing based on total body weight may lead to over dosing of obese patients. Oseltamivir phosphate (Tamiflu®) is an antiviral agent that is currently dosed as 75 mg once daily for chemoprophylaxis and twice daily for treatment of influenza in adults.
Oseltamivir is rapidly converted to its active metabolite, oseltamivir carboxylate by esterases. The clearance of oseltamivir carboxylate is dependent on tubular secretion and glomerular filtration. Given that these drug elimination pathways may be enhanced in obese individuals, oseltamivir carboxylate plasma exposures may be lower in obese subjects compared to normal weight subjects. Although a specific plasma exposure target for oseltamivir carboxylate has not been established, lower oseltamivir carboxylate exposures may predispose obese patients to treatment failure and increase the probability for emergence of oseltamivir-resistant influenza virus. The current study proposes to characterize the plasma oseltamivir carboxylate concentration-time profile after single and multiple doses of oral oseltamivir in a cohort of healthy morbidly obese subjects. The study will be performed using a phase 1, open-label,single and multiple dose, pharmacokinetic study design in twenty obese adult subjects. This pilot study will provide pharmacokinetic data that may be incorporated into existing oseltamivir carboxylate population pharmacokinetic models to define appropriate doses of oseltamivir in obese patients.
|United States, New Jersey|
|Paramaus, New Jersey, United States, 07652|
|Principal Investigator:||Manjunath Pai, PharmD||ACPHS|