THE EFFECTS OF EPOPROSTENOL ON DRUG DISPOSITION .2. A PILOT-STUDY OF THE PHARMACOKINETICS OF FUROSEMIDE WITH AND WITHOUT EPOPROSTENOL IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

The effect of epoprostenol on the pharmacokinetics of furosemide was i nvestigated in 23 patients with end-stage congestive heart failure (CH F) receiving conventional therapy alone or conventional therapy plus e poprostenol. Estimates of the apparent oral clearance, volume of distr ibution, and absorption rate constant for furosemide were generated fr om 198 serum furosemide concentrations using nonlinear mixed effects m odeling (NONMEM), Univariate analyses were performed to assess the eff ects of patient factors on the apparent oral clearance of furosemide. The final multivariate model determined by backwards elimination inclu ded concomitant digoxin therapy. When concomitant epoprostenol therapy was included in the final model, there was a 13% decrease in the appa rent oral clearance of furosemide in response to short-term administra tion of epoprostenol. However, the effect of concomitant epoprostenol therapy was not statistically significant and was no longer apparent b y the end of the 12-week study. These data suggest that epoprostenol m ay have a slight short-term effect on the pharmacokinetics of furosemi de; the interaction between epoprostenol and furosemide is not clinica lly significant, however.