Effect of concomitant food intake on absorption kinetics of fenoldopam (SK&F 82526) in healthy volunteers.
Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.
D000328:Adult; D001552:Benzazepines / Q000378:metabolism*; D001682:Biological Availability; D004435:Eating; D005260:Female; D018818:Fenoldopam; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D014665:Vasodilator Agents / Q000378:metabolism*
D001552:Benzazepines; D014665:Vasodilator Agents; D018818:Fenoldopam