Plasma protein binding of zolpidem in liver and renal insufficiency.

Similar degree (65-66%) of binding of zolpidem (0.1 microgram/ml) was found with physiological concentrations of isolated human albumin (40 g/l) or alpha-1-acid glycoprotein (1 g/l). Zolpidem binding was studied in plasma from 6 healthy subjects, 12 patients with renal failure, 12 patients with liver cirrhosis and 12 chronic uremics maintained on hemodialysis as well as in 12 serum samples from the placental cord. The unbound fraction (mean +/- s.e.m.) was 8.1 +/- 0.2% (healthy volunteers), 10.8 +/- 0.4% (renal failure), 11.3 +/- 0.7% (liver cirrhosis); 14.9 +/- 1.0% (before hemodialysis); 9.8 +/- 0.4% (after hemodialysis) and 13.2 +/- 0.9% (placental cord). All values, except those after hemodialysis, were significantly different (Dunnett's test) from those of the volunteers. Hemodialysis significantly increased the binding of zolpidem in plasma. The kinetics of protein binding of zolpidem were investigated in plasma samples from 3 healthy subjects. The average number of binding sites was 1.83 x 10(-7) mol per gram protein and the average association constant was 4.49 x 10(5) M-1.