Summary
Plasma levels and urinary excretion of the dopamine agonist, transdihydrolisuride (TDHL), were measured by radioimmunoassay in healthy male volunteers given TDHL 50 µg i.v. and oral doses of 200, 400 and 800 µg. 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±0.4 l/kg. The bioavailability of oral TDHL was proportional to the dose; after 200, 400 and 800 µg 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 µg, 400 µg and 800 µg. The effect lasted for more than 12 h after the lowest dose and for more than 24 h after 400 and 800 µg. Side effects, mainly nausea and headache, only occurred at the two highest dose levels.
Similar content being viewed by others
References
Wachtel H, Dorow R (1983) Dual action on central dopamine function of transdihydrolisuride, a 9,10-dihydrogenated analogue of the ergot dopamine agonist lisuride. Life Sci 32: 421–432
Kehr W, Speckenbach W (1978) Effect of lisuride and LSD on monoamine synthesis after axotomy or reserpine treatment in rat brain. Naunyn-Schmiedebergs Arch Pharmacol 301: 163–169
Horowski R, Wendt H, Gräf K-J (1978) Prolactin-lowering effect of low doses of lisuride in man. Acta Endocrinol 87: 234–240
Auskova M, Rezabek K, Zikan V, Semonsky M (1974) Laktationshemmende Wirkung von N-(D-6-Methyl-8-isoergolin-I-yl)-N′,N′-diäthylharnstoff (VÜFB-6638). Experientia 30: 393–394
Sinhay YN, Shelby FW, Lewis UJ, van der Laan WP (1973) Homologous radioimmunoassay for human prolactin. J Clin Endocrinol 36: 506–516
Hümpel M, Nieuweboer B, Hasan SH, Wendt H (1981) Radioimmunoassay of plasma lisuride in man following intravenous and oral administration of lisuride hydrogen maleate; effect on plasma prolactin level. Eur J Clin Pharmacol 20: 47–51
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Krause, W., Dorow, R., Nieuweboer, B. et al. Pharmacokinetics and pharmacodynamics of the ergot derivative, transdihydrolisuride, in man. Eur J Clin Pharmacol 27, 335–339 (1984). https://doi.org/10.1007/BF00542171
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00542171