title: Pharmacokinetics of oseltamivir in young and very elderly subjects.
abstract: BACKGROUND
  Pharmacokinetic studies of oseltamivir in very elderly patients (> or = 80 y) have not previously been performed.
  
  
  OBJECTIVE
  To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects.
  
  
  METHODS
  Young (20-35 y, fasting, n = 7) and very elderly subjects (> or = 80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed.
  
  
  RESULTS
  The time to maximum plasma concentration (tmax) for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (Cmax) and AUC(inf) were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, Cmax and AUC(inf) values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the Cmax values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups.
  
  
  CONCLUSIONS
  Exposures (AUC(inf)) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.
authors.affiliation: Department of Clinical Pharmacology, Chugai Clinical Research Center Co. Ltd, Tokyo, Japan. abemsi@chugai-pharm.co.jp
authors.forename: Masaichi
authors.initials: M
authors.lastname: Abe
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: Akinori
authors.initials: A
authors.lastname: Urae
authors.forename: Joanne
authors.initials: J
authors.lastname: Barrett
authors.forename: Haruki
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rayner
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D053139:Oseltamivir / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir