The Effects of Epoprostenol on Drug Disposition II: 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 investigated in 23 patients with end-stage congestive heart failure (CHF) receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of the apparent oral clearance, volume of distribution, and absorption rate constant for furosemide were generated from 198 serum furosemide concentrations using nonlinear mixed effects modeling (NONMEM). Univariate analyses were performed to assess the effects of patient factors on the apparent oral clearance of furosemide. The final multivariate model determined by backwards elimination included concomitant digoxin therapy. When concomitant epoprostenol therapy was included in the final model, there was a 13% decrease in the apparent oral clearance of furosemide in response to short-term administration of epoprostenol. However, the effect of concomitant epoprostenol therapy was not statistically significant and was no longer apparent by the end of the 12-week study. These data suggest that epoprostenol may have a slight short-term effect on the pharmacokinetics of furosemide; the interaction between epoprostenol and furosemide is not clinically significant, however.