In two groups of volunteers pharmacological parameters of the antihypotensive
drug midodrine have been investigated. The first group of 12 male healthy volunteers received 2.5 mg
midodrine hydrochloride intravenously, as drinking
solution or as
tablet according to a randomized cross-over design. Plasma and urine samples were analyzed for
midodrine and its main metabolite
ST 1059 by high-performance liquid chromatography. The mean maximum concentration in plasma for
midodrine was 10 ng/ml 20-30 min after
oral administration, for
ST 1059 5 ng/ml after 1 h.
Midodrine was eliminated with a terminal half-life of 0.5 h,
ST 1059 with a half-life of 3 hrs. The mean area under the plasma-level vs. time curve (AUC) of
ST 1059 after administration of 2.5 mg
midodrine i.v. was 28.7 ng x h/ml, and similar for the other formulations which are considered to be bioequivalent. In a second group of 15 volunteers with
postural hypotension midodrine (M) as alpha-
sympathomimetic drug and
oxilofrine (O) as beta-
sympathomimetic drug was given i.v. in a randomized double blind study against placebo (P). Blood pressure (BP), heart rate (HR) and circulating
catecholamines (CA) were determined before and after
injections of the drugs as well as before and during 10 min of tilting. Echocardiographic parameters were obtained at rest before and after the administration of the drugs. Blood pressure remained unchanged at rest and during
orthostasis after all agents injected. After
oral administration of
midodrine heart rate was decreased and systolic blood pressure increased significantly and dose-dependently. M lowered circulating
noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)