title: Infusions of albumin increase free fraction of naproxen in healthy volunteers: a randomized crossover study.
abstract: BACKGROUND
  In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical-grade albumin influence the albumin-binding capacity for highly protein-bound drugs. However, the half-life of the stabilizers and the quantitative effect have been difficult to determine.
  
  
  METHODS
  A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N-acetyl-DL-tryptophan, caprylate, and naproxen.
  
  
  RESULTS
  The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N-acetyl-DL-tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N-acetyl-DL-tryptophan had a half-life of approximately 30 min. The half-life of caprylate was <15 min.
  
  
  CONCLUSIONS
  A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free-fraction naproxen decreased together with the detectable levels of the stabilizers N-acetyl-DL-tryptophan and caprylate. N-acetyl-DL-tryptophan and caprylate have a short half-life in serum.
authors.affiliation: Division of Anaesthesia and Intensive Care, Oslo University Hospital, Oslo, Norway. pal.aarstrand.reine@rikshospitalet.no
authors.forename: P A
authors.initials: PA
authors.lastname: Reine
authors.forename: U E
authors.initials: UE
authors.lastname: Kongsgaard
authors.forename: A
authors.initials: A
authors.lastname: Andersen
authors.forename: A-K
authors.initials: AK
authors.lastname: Thøgersen
authors.forename: H
authors.initials: H
authors.lastname: Olsen
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002210:Caprylates / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000493:pharmacokinetics*; D010592:Pharmaceutic Aids; D016896:Treatment Outcome; D014364:Tryptophan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002210:Caprylates; D007202:Indicators and Reagents; D010592:Pharmaceutic Aids; C006392:N-acetyltryptophan; D009288:Naproxen; D014364:Tryptophan