Improved orthostatic dysregulation record after administration of a sustained-release form of urapidil

The efficacy and safety of urapidil has been demonstrated in a long-term treatment. However, a relatively good record of side effects has been marred by reports of orthostatic dysregulation. This study was designed to examine the blood pressure lowering effect, tolerability and pharmacokinetics of a sustained-release formulation of urapidil. Twelve patients received either 60 mg of sustained-release urapidil (Ebrantil 60) or 50 mg urapidil for experimental reference as a fast-release tablet in single or multiple doses in a randomized, double-blind fashion. To ensure the double blind-character of the study, the tablets were encapsulated. Blood samples for the determination of urapidil (HPLC) were drawn before and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h post application. Blood pressure was measured at 0.5, 1.5, 3, 8, 10 and 12 h post application. An orthostatic test was performed before and at 1, 2, 4 and 6 h post application. Twelve h after the first application, patients received a second capsule or encapsulated tablet and continued medication for two days. On day four, the same procedure as on day one was repeated, except that patients received no evening medication and blood samples and blood pressure were measured at 24, 28 and 32 h post application on the fifth day. The Cmax of sustained-release urapidil was 44% lower than for the single tablet dose and 37% lower after multiple dosing. The peak-trough fluctuation of the steady-state serum concentrations was 29% lower for the sustained-release capsule (138 +/- 45%) compared to the tablet (195 +/- 83%).(ABSTRACT TRUNCATED AT 250 WORDS)