Pharmacokinetics and Pharmacodynamics of Tamsulosin in its Modified-Release and Oral Controlled Absorption System Formulations.

Tamsulosin is an α1-adrenoceptor antagonist used for the treatment of lower urinary tract symptoms that are suggestive of benign prostatic hyperplasia. It is mostly used in a modified-release (MR) formulation, but an oral controlled absorption system (OCAS) and a `without-water' tablet formulation are also available in some countries. The oral bioavailability of the MR formulation in the fasted state is close to 100%. Whereas absorption from the MR formulation is affected by concomitant food intake, that of the OCAS formulation is food independent. Tamsulosin exhibits high plasma-protein binding, largely to α1-acid glycoprotein. It is metabolized, mainly by cytochrome P450 (CYP) 3A4 and CYP2D6 to compounds with low abundance, and 8.7-15% of an oral dose is excreted renally as the parent compound. The pharmacokinetics of tamsulosin are not affected to a major extent by age, and pharmacokinetic alterations in renally impaired patients relate largely to an increased concentration of α1-acid glycoprotein. Pharmacokinetic alterations with hepatic impairment are also only moderate, thus neither renal nor mild to moderate hepatic impairment necessitates dose adjustment. Concomitant exposure to potent CYP3A4 inhibitors can more than double the exposure of tamsulosin. Clinical studies have indicated that despite its lower bioavailability, the OCAS formulation has the same treatment efficacy as the MR formulation but causes somewhat fewer cardiovascular adverse effects. [ABSTRACT FROM AUTHOR]