EFFECTS OF IBOPAMINE ON POSTURAL HYPOTENSION IN PURE AUTONOMIC FAILURE

We wished to determine whether ibopamine, a dopaminergic prodrug with weak agonist activity on alpha-and beta-adrenoceptors, improves orthos tatic tolerance in autonomic insufficiency. Three subjects with severe orthostatic hypotension resulting from pure autonomic failure (PAF) w ere studied. Direct arterial blood pressure (ABP) and heart rate (HR) were recorded continuously. Orthostatic tolerance was evaluated by 60- degrees passive head-up tilting. Tilting was performed before and afte r a single oral 100-mg dose of ibopamine. Blood samples for measuremen t of plasma catecholamines, free epinine (the active metabolite of ibo pamine), and conjugated epinine were taken at regular intervals. In al l 3 subjects, orthostatic tolerance was greatly improved by ibopamine. This improvement occurred as soon as 10-30 min after administration o f ibopamine and lasted 20-50 min. Alpha-Adrenoceptor blockade with phe ntolamine abolished the effect of ibopamine. The interindividual pharm acokinetics of ibopamine varied considerably: Peak plasma concentratio ns of ibopamine in the three subjects were 2.8, 4.5, and 35.4 ng/ml, r espectively. The high level of epinine in one patient was associated w ith severe hypertension and tachycardia. ibopamine may be a valuable n ew pharmacologic treatment for orthostatic hypotension in PAF, but in light of the highly variable interindividual pharmacokinetics further studies must be performed before use of the compound can be advocated in this disorder.