Pharmacokinetics and pharmacodynamics of the ergot derivative, transdihydrolisuride, in man.

Plasma levels and urinary excretion of the dopamine agonist, transdihydrolisuride (TDHL), were measured by radioimmunoassay in healthy male volunteers given TDHL 50 micrograms i.v. and oral doses of 200, 400 and 800 micrograms. Plasma prolactin was also measured by radioimmunoassay. Following i.v. injection, the concentration of TDHL declined with a half-life of 37 +/- 19 min. The total clearance was 38 +/- 27 ml/min/kg and the apparent volume of distribution was 1.3 +/- 0.41/kg. The bioavailability of oral TDHL was proportional to the dose; after 200, 400 and 800 micrograms the bioavailability was 20 +/- 25%, 31 +/- 24% and 48 +/- 26%. TDHL was almost totally metabolized and less than 0.5% of the dose was excreted unchanged in urine in 24 h. Plasma prolactin levels were depressed by 66 +/- 15%, 75 +/- 11% and 80 +/- 7% after TDHL 200 micrograms, 400 micrograms and 800 micrograms. The effect lasted for more than 12 h after the lowest dose and for more than 24 h after 400 and 800 micrograms. Side effects, mainly nausea and headache, only occurred at the two highest dose levels.