Human pharmacology of urapidil

Abstract

Urapidil is a phenylpiperazine-substituted uracil derivative used in hypertension. It is rapidly absorbed when given by mouth. Peak blood concentrations of the slow release capsule occur 4 to 6 hours after administration. Oral bioavailability is 78% (range 72 to 84%) and distribution half-life and terminal half-life are about 35 minutes and 3 hours, respectively. Plasma clearance is 12 L/h and renal clearance 1.8 L/h. Seventeen percent appears in urine as the parent compound within 24 hours of dosing. There is extensive hepatic metabolism to the parahydroxylated (34% in urine). N-demethylated (4% in urine) and O-demethylated (3% in urine) products. Elimination is not saturable at usual clinical doses. The major action of urapidil is post-synaptic alpha 1-adrenergic blockade, with a minor degree of beta 1-adrenergic blockade and a centrally mediated reduction in sympathetic outflow which has an as yet unidentified basis.