| pubmed-article:3533566 | pubmed:abstractText | In a double-blind, interindividual comparative study 30 healthy volunteers were randomly allocated to oral treatment with 5 or 10 mg of dihydroergotamine (DHE) or placebo once daily for 16 days. Regional basic venous blood volume (BBV), pressure dependent venous capacitance (CV) of the calf, resting heart rate and blood pressure were determined on Days 1 and 15 of treatment. Plasma concentrations of DHE were monitored on Days 2 and 16. Due to spontaneous vasodilation BBV varied considerably, showing that it is an inappropriate parameter for investigating the venoconstrictor activity of DHE. CV remained unchanged after the first dose of DHE but it had declined significantly on both dosage regimens at the end of the treatment phase. In contrast, the blood concentration profiles of DHE were comparable at the beginning and the end of the trial. The discrepancy can best be explained by the existence of an effect compartment, e.g. smooth vascular musculature, which slowly becomes filled with DHE and/or its active metabolites. The venoconstrictor activity of DHE exhibited a significant dose-response relationship. | lld:pubmed |
