title: Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers.
abstract: The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.
authors.affiliation: Rheumatological Department, University Hospital, Hvidovre, Denmark.
authors.forename: P C
authors.initials: PC
authors.lastname: Gøtzsche
authors.forename: F
authors.initials: F
authors.lastname: Andreasen
authors.forename: C
authors.initials: C
authors.lastname: Egsmose
authors.forename: B
authors.initials: B
authors.lastname: Lund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004232:Diuretics / Q000627:therapeutic use; D004415:Dyspepsia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D009288:Naproxen / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D004232:Diuretics; D012709:Serum Albumin; D009288:Naproxen