Studies on the Clinical Pharmacology of Prazosin. II: The Influence of Indomethacin and of Propranolol on the Action and Disposition of Prazosin

1 The possibility of pharmacodynamic and pharmacokinetic interactions of prazosin with indomethacin and with propranolol have been studied in healthy subjects. 2 In four out of nine individuals indomethacin considerably attenuated prazosin-induced hypotension, but noradrenaline concentrations were unchanged from the day when blood pressure fell greatly. The effect of prazosin in the other five subjects was not influenced by indomethacin. 3 Indomethacin prevented the rise in plasma renin activity seen following administration of prazosin alone. 4 Propranolol did not prevent the syncope associated with the first dose of prazosin. 5 Propranolol affected neither the absorption nor elimination of prazosin. 6 It is concluded that in certain subjects indomethacin can largely prevent the hypotensive effect of parazosin, possible by increasing adrenergic receptor sensitivity. The theoretical possibility that propranolol could influence prazosin disposition or syncope was not substantiated.