The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS ®)

Abstract

Context: A new formulation of tamsulosin for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) has been developed. This formulation uses the proprietary oral controlled absorption system (OCAS ®) technology which has the potential to better control the release during passage of the gastrointestinal tract including the colon and which may be devoid of a food effect. This study describes the characteristics of the tamsulosin OCAS formulation with respect to single and multiple dose human pharmacokinetics (PK). Methods: The single dose PK of three tamsulosin OCAS 0.4 mg formulations (S2, S3 and S4) in comparison with tamsulosin modified release (MR) 0.4 mg capsules were analysed in 12 young healthy volunteers in a 4-way crossover study to allow selection of a candidate for further development. 24 young healthy volunteers were subsequently recruited to compare multiple dose PK for tamsulosin OCAS 0.4, 0.8 and 1.2 mg S3 formulation under fasted conditions with tamsulosin OCAS 0.4 mg under fed conditions in a 4-way crossover study. Results: The tamsulosin OCAS S3 formulation was selected for further development. This chosen formulation shows distinctively different PK from the commercially available tamsulosin MR capsules with a lower maximum plasma concentration ( C max), a slightly lower area under the curve (AUC) and reduced fluctuation in 24-hour plasma concentrations/improved C max/ C 24h ratio while showing dose linearity and an unchanged elimination half-life. It will allow once daily dosing in the treatment of LUTS/BPH. In addition, tamsulosin OCAS does not have a food effect unlike the MR capsules. Conclusions: Tamsulosin OCAS shows improved PK compared with the standard MR capsules. Such improved PK may translate in an improvement of the efficacy/safety ratio during the treatment of LUTS/BPH. Demonstration of such potential benefits as well as the establishment of the daily dose will require subsequent confirmatory clinical studies.