Plasma protein binding of furosemide in kidney transplant patients

The present investigation was undertaken in order to determine the in vivo plasma protein binding of furosemide in kidney transplant patients and its possible consequence on furosemide effect. Using an equilibrium dialysis technique, serial plasma samples of furosemide taken after intravenous administration were dialyzed against an equal volume of isotonic Krebs Ringer bicarbonate buffer (pH 7.4). Dialysis was performed at 37 degrees C for 5 hr, and furosemide concentrations (total as well as free) were analyzed by HPLC using fluorescence detection. It was observed that kidney transplant patients on concomitant sulfisoxazole treatment (KT+) had a significantly greater value for percent free of furosemide as compared to transplant patients not on sulfisoxazole (KT-) (4.4 +/- 0.8 for KT+ vs. 1.7 +/- 0.3% for KT-; p less than 0.01) as well as to healthy volunteers (4.4 +/- 0.8 for KT+ vs. 1.2 +/- 0.2% for controls; p less than 0.01). In addition, kidney transplant patients not on concomitant sulfisoxazole treatment had a significantly higher value for percent free of furosemide with respect to healthy volunteers (p less than 0.05). Nonlinear plasma protein binding was also observed for one patient, who had values for percent free of furosemide ranging from 1.3 to 12.9%. However, no significant correlation was found between the fraction of the dose excreted unchanged in the urine and percent free of furosemide.