PHARMACOKINETIC PARAMETERS AND HEMODYNAMIC ACTIONS OF MIDODRINE IN YOUNG VOLUNTEERS

In two groups of volunteers pharmacological parameters of the antihypo tensive drug midodrine have been investigated. The first group of 12 m ale healthy volunteers received 2.5 mg midodrine hydrochloride intrave nously, as drinking solution or as tablet according to a randomized cr oss-over design. Plasma and urine samples were analyzed for midodrine and its main metabolite ST 1059 by high-performance liquid chromatogra phy. 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. ti me 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 wi th postural hypotension midodrine (M) as alpha-sympathomimetic drug an d oxilofrine (O) as beta-sympathomimetic drug was given i.v. in a rand omized double blind study against placebo (P). Blood pressure (BP), he art rate (HR) and circulating catecholamines (CA) were determined befo re and after injections of the drugs as well as before and during 10 m in of tilting. Echocardiographic parameters were obtained at rest befo re and after the administration of the drugs. Blood pressure remained unchanged at rest and during orthostasis after all agents injected. Af ter oral administration of midodrine heart rate was decreased and syst olic blood pressure increased significantly and dose-dependently. M lo wered circulating noradrenaline. Echocardiographic parameters were cha nged after administration of M (increase in end-diastolic volume index and SVI) and O (increase in SVI, EF and cardiac index). The observed changes in sympathetic and cardiovascular parameters are in agreement with the sympathomimetic actions of the drugs investigated and allow a differential therapeutic classification: M is suitable for patients w ith sympathotonic orthostatic reaction; O should be recommended for pa tients with asympathotonic orthostatic reaction.