Abstract
Plasma binding data were generated for the nonsteroidal antiinflammatory drug, napproxen, by equilibrium dialysis. Plasma samples were obtained from 7 healthy volunteers, from 43 uremic patients and from a blood bank. Drug in plasma was equilibrated with buffer across a suitable membrane. Buffer and plasma compartments were analysed by HPLC for free and total naproxen concentrations. Creatinine, urea and albumin plasma levels were determined by suitable methods. Binding of naproxen to healthy plasma exceeded 99% at concentrations attained in therapy. Free naproxen fraction was consistantly higher in uremic plasma with binding values ranging from 89-99%. The correlations examined indicated a dependence of naproxen free fraction on the degree of renal impairment, indicated by creatinine and urea plasma levels. Binding of naproxen was independent of albumin concentration at plasma albumin levels higher than 15 g/1. Apart from disease, plasma binding of naproxen was also perturbed, but to a lesser degree, by some other nonsteroidal antiinflammatory drugs such as flufenamic acid and aspirin.
The results of the present study indicate that plasma binding of naproxen is impaired in patients suffering from chronic renal failure of different genesis.