Factors affecting serum protein binding of phenytoin, diazepam and propranolol in acute renal diseases.

The effect of acute renal disease on the serum free fraction of phenytoin, diazepam and propranolol was examined in vitro among 37 patients with acute renal insufficiency of varying etiology and 10 healthy control subjects, men and women equally. The free fractions were separated at 37 degrees C using a pressure ultrafiltration method. The free fraction of phenytoin varied from about 14% to 45% and that of diazepam from 2% to 10%. The free fraction did not correlate significantly with either the serum urea or creatinine concentrations or the creatinine clearance within the acutely uremic group. The free fractions of propranolol varied considerably in the uremic patients but did not correlate significantly with the above parameters either. The mean free fractions of propranolol in the acutely uremics (11.9 +/- 1.0%, mean +/- SE) and controls (8.9 +/- 0.5%) did not differ significantly. The free fractions of both phenytoin and diazepam had a significant inverse correlation with the serum albumin level and that of propranolol with the alpha 1-acid glycoprotein (alpha, AGP) level. The correlations were similar irrespective of the etiology of renal failure. In practice, the variable best predicting the phenytoin and diazepam free fractions in acute renal insufficiency is the serum albumin concentration, and for propranolol the serum alpha 1-AGP concentration.