Investigation of the therapeutic equivalence of different galenical preparations of O-(beta-hydroxyethyl)-rutosides following multiple dose peroral administration

Abstract

Oxerutins (O-(beta-hydroxyethyl)-rutosides, HR, Venoruton) are available in different releasing galenical formulations for the treatment of chronic venous insufficiency (CVI). In order to investigate the biopharmaceutical relevance of the releasing properties of the galenical forms the therapeutic efficacy between the commercially available forms was investigated (500 mg sustained release film tablets, 300 mg sustained release film tablets, 300 mg normally releasing capsules) in comparison to an aqueous solution and placebo. In total 100 female patients with CVI grade II participated. The study was carried out following a randomized, placebo controlled design with parallel treatment groups. Following a two-week run-in phase patients were treated for 12 weeks with different posologies of HR (2 x 1/d 500 mg, 3 x 1/d 300 mg, 1 x 1000 mg/d as aqueous solution). Main criterion was the reduction of leg volume following 12 weeks treatment. Subjective criteria were descriptively evaluated. All four HR treatments were significantly superior to placebo (p < 0.0008). The different posologies had no influence on the efficacy. The therapeutic efficacy is independent of the in vitro rate of release. The available forms are regarded as bioequivalent.