title: Oseltamivir pharmacokinetics in morbid obesity (OPTIMO trial).
abstract: BACKGROUND
  Detailed pharmacokinetics to guide oseltamivir (Tamiflu®) dosing in morbidly obese patients is lacking.
  
  
  METHODS
  The OPTIMO trial was a single-centre, non-randomized, open-label pharmacokinetic study of single-dose and steady-state oral oseltamivir phosphate and its carboxylate metabolite in healthy, morbidly obese [body mass index (BMI) >  40)] and healthy, non-obese (BMI  <  30) subjects.
  
  
  RESULTS
  In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir oral clearance (CL/F) [840 (range 720-1640) L/h versus 580 (470-1800) L/h] was higher, the area under the curve from time zero to infinity (AUC(0-∞)) [89 (46-104) ng·h/mL versus 132 (42-160) ng·h/mL] was lower and the volume of distribution (V/F) [2320 (900-8210) L versus 1670 (700-7290) L] was unchanged. In the morbidly obese versus control subjects, respectively, the single-dose median oseltamivir carboxylate CL/F [22 (17-40) L/h versus 23 (12-33) L/h], AUC(0-∞) [3100 (1700-4100) ng·h/mL versus 3000 (2100-5900) ng·h/mL] and V/F [200 (130-370) L versus 260 (150-430) L] were similar. Similar results for oseltamivir and oseltamivir carboxylate CL/F, AUC₀₋₁₂ and V/F values were observed in the multiple-dose study.
  
  
  CONCLUSIONS
  With single and multiple dosing, the systemic exposure to oseltamivir is decreased but that of oseltamivir carboxylate is largely unchanged. Based on these pharmacokinetic data, an oseltamivir dose adjustment for body weight would not be needed in morbidly obese individuals.
authors.affiliation: College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada B3H4R2. lucas@dal.ca
authors.forename: L M
authors.initials: LM
authors.lastname: Thorne-Humphrey
authors.forename: K B
authors.initials: KB
authors.lastname: Goralski
authors.forename: K L
authors.initials: KL
authors.lastname: Slayter
authors.forename: T F
authors.initials: TF
authors.lastname: Hatchette
authors.forename: B L
authors.initials: BL
authors.lastname: Johnston
authors.forename: S A
authors.initials: SA
authors.lastname: McNeil
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D015992:Body Mass Index; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D053139:Oseltamivir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011355:Prodrugs / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D053139:Oseltamivir