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Infusions of albumin increase free fraction of naproxen in healthy volunteers: a randomized crossover study
Author(s) -
REINE P. A.,
KONGSGAARD U. E.,
ANDERSEN A.,
THØGERSEN A.K.,
OLSEN H.
Publication year - 2010
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2009.02142.x
Subject(s) - naproxen , albumin , medicine , crossover study , free fraction , tryptophan , serum albumin , pharmacology , plasma protein binding , biochemistry , chemistry , pathology , amino acid , alternative medicine , placebo
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. Method: 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. Conclusion: 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.