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

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Abstract

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.

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Acknowledgements

The authors thank Mr Walter Krauwinkel (Astellas Europe BV, Leiderdorp, the Netherlands) for his helpful comments on this manuscript.

Work in the authors’ laboratory has been supported in part by Astellas and Boehringer Ingelheim. Martin C. Michel has received research support, and lecture and consultancy honoraria related to tamsulosin from Astellas and Boehringer Ingelheim, as well as lecture honoraria from Schwarz Pharma. Gabriela Franco-Salinas and Jean J.M.C.H. de la Rosette have no conflicts of interest that are directly relevant to the contents of this review.

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Authors and Affiliations

  1. Department of Pharmacology & Pharmacotherapy, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Gabriela Franco-Salinas &  Martin C. Michel

  2. Department of Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Jean J. M. C. H. de la Rosette

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  1. Gabriela Franco-Salinas
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  2. Jean J. M. C. H. de la Rosette
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Correspondence to Martin C. Michel.

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Franco-Salinas, G., de la Rosette, J.J.M.C.H. & Michel, M.C. Pharmacokinetics and Pharmacodynamics of Tamsulosin in its Modified-Release and Oral Controlled Absorption System Formulations. Clin Pharmacokinet 49, 177–188 (2010). https://doi.org/10.2165/11317580-000000000-00000

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