ABSTRACTObesity is an independent risk factor for mortality in patients infected with pandemic influenza A virus (H1N1). Given the poor outcomes observed among adult obese patients with H1N1, the dosing of antiviral agents in this population has been questioned, and use of twice the standard oseltamivir dose has been suggested. However, studies evaluating the disposition of oseltamivir and oseltamivir carboxylate (the active metabolite) in the obese population are scant. We evaluated the single-dose and steady-state pharmacokinetics of oseltamivir (75 mg by mouth twice daily) in a cohort of 21 healthy adult volunteers with class III obesity (body mass index [BMI], ≥40 kg/m2). The median (minimum, maximum) age, weight, and BMI were 36 (19, 50) years, 122 (106, 159) kg, and 43.7 (40.0, 54.4) kg/m2, respectively. The population pharmacokinetic exposure profiles of oseltamivir carboxylate (the active metabolite) were comparable between class III obese subjects and nonobese adults (healthy and infected). Similar to previous pharmacokinetic analyses in nonobese subjects, the mean (percent covariance [CV]) area under the concentration-time curve for the dosing interval (AUC0–τ) was 2,621 ng·h/ml (17) for oseltamivir carboxylate. Body size was significantly (P< 0.05) associated with oseltamivir and oseltamivir carboxylate apparent clearance, but the correlation coefficient was poor (R2≤ 0.3). Creatinine clearance estimated by the Cockcroft-Gault method and lean body weight were also significantly (P< 0.05) but poorly (R2= 0.17) correlated with oseltamivir carboxylate apparent clearance. Since the systemic exposure of oseltamivir carboxylate is not reduced in class III obese adults with standard doses, a dose increment of oseltamivir is likely to be unnecessary.
Oseltamivir Carboxylate, the Active Metabolite of Oseltamivir Phosphate (Tamiflu), Detected in Sewage Discharge and River Water in Japan
