tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2011 Sep 19. [Epub ahead of print]
Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight is not Necessary.
Pai MP, Lodise TP Jr.
Source
Albany College of Pharmacy and Health Sciences, Albany, NY.
Abstract
Obesity is an independent risk factor for mortality in patients infected with pandemic influenza A (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 (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/m(2)). The median [min, max] age, weight and BMI were: 36 (19, 50) years, 122 (106, 159) kg, and 43.7 [40.0, 54.4] kg/m(2), respectively. The population pharmacokinetic exposure profiles of oseltamivir carboxylate (active metabolite) are comparable between class III obese subjects and non-obese adults (healthy and infected). Similar to previous pharmacokinetic analyses in non-obese subjects, the mean (%CV) area under the curve for the dosing interval (AUC(0-τ)) was 2621 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 (R(2) ≤ 0.3). Creatinine clearance estimated by Cockcroft-Gault and lean body weight was also significantly (p<0.05) but poorly (R(2)= 0.17) correlated to 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.
PMID:
21930881
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21930881
Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight is not Necessary.
Pai MP, Lodise TP Jr.
Source
Albany College of Pharmacy and Health Sciences, Albany, NY.
Abstract
Obesity is an independent risk factor for mortality in patients infected with pandemic influenza A (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 (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/m(2)). The median [min, max] age, weight and BMI were: 36 (19, 50) years, 122 (106, 159) kg, and 43.7 [40.0, 54.4] kg/m(2), respectively. The population pharmacokinetic exposure profiles of oseltamivir carboxylate (active metabolite) are comparable between class III obese subjects and non-obese adults (healthy and infected). Similar to previous pharmacokinetic analyses in non-obese subjects, the mean (%CV) area under the curve for the dosing interval (AUC(0-τ)) was 2621 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 (R(2) ≤ 0.3). Creatinine clearance estimated by Cockcroft-Gault and lean body weight was also significantly (p<0.05) but poorly (R(2)= 0.17) correlated to 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.
PMID:
21930881
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21930881