Comparison of Vascular α 1-Adrenoceptor Antagonism of Tamsulosin in Oral Controlled Absorption System (OCAS) and Modified Release (MR) Formulations

Abstract

Objective: The cardiovascular α 1-adrenoceptor (AR) antagonism of the new oral controlled absorption system (OCAS) 0.4 mg tablet formulation of tamsulosin was compared with that of the modified release (MR) 0.4 mg capsule formulation in healthy male volunteers after a single dose in the fasted state. Methods: Eighteen healthy volunteers were to be randomised in a 3-way, cross-over study consisting of three one day study periods. On each study day one of the following treatments was tested: placebo, tamsulosin OCAS 0.4 mg tablet or tamsulosin MR 0.4 mg capsule. The cardiovascular α 1-AR antagonism was assessed by measuring the inhibition of phenylephrine (PE)-induced increases in diastolic blood pressure (DBP) and total peripheral resistance (TPR) 2 hours before and 2, 4, 6, 8 and 10 hours after dosing with the test drug. Additionally, the pharmacokinetics (PK) and adverse events (AEs) were assessed. Results: Eighteen healthy volunteers (mean age 29.9 years) were enrolled. Two of the 18 subjects discontinued the study; one because of an AE and one was lost to follow up. Tamsulosin OCAS 0.4 mg tablets showed a lower maximum plasma concentration (mean C max: 6.4 vs. 18.6 ng/ml) but a similar time to C max (approximately 6 hours) relative to tamsulosin MR 0.4 mg capsules. This was accompanied by less inhibition of PE-induced increases in DBP and TPR for tamsulosin OCAS 0.4 mg tablets than for tamsulosin MR 0.4 mg capsules at all post-dose time points; these differences were statistically significant ( p ≤ 0.05) at all but the 2 hour post-dose time point for TPR. There were no apparent differences in AEs between the two formulations. Conclusions: Tamsulosin OCAS 0.4 mg tablets show less cardiovascular α 1-AR antagonism, i.e. less inhibition of vasoconstriction and total peripheral resistance, than tamsulosin MR 0.4 mg capsules following single dosing in fasting healthy volunteers. This is most likely related to reduced drug exposure by the OCAS formulation. The data indicate that on an empty stomach tamsulosin OCAS may provide a better cardiovascular safety profile than tamsulosin MR.