Pharmacokinetics of Oseltamivir Carboxylate In Morbidly Obese Subjects
| Status: | Archived |
|---|---|
| Conditions: | Obesity Weight Loss |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | July 2010 |
| End Date: | June 2011 |
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.
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.
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