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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References
Barendrecht MM, Abrams P, Schumacher H, et al. Do α1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance? Neurourol Urodyn 2008; 27: 226–30
McConnell JD, Roehrborn CG, Bautista O, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. New Engl J Med 2003; 349: 2387–98
Roehrborn CG, Schwinn DA. α1-Adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 2004; 171: 1029–35
Hieble JP, Bylund DB, ClarkeDE, et al. International Union ofPharmacology: X. Recommendation for nomenclature of a1-adrenoceptors: consensus update. Pharmacol Rev 1995; 47: 267–70
Michel MC, Kenny BA, Schwinn DA. Classification of α1-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol 1995; 352: 1–10
Michel MC, Vrydag W. α1-, α2- and b-adrenoceptors in the urinary bladder, urethra and prostate. Br J Pharmacol 2006; 147: S88–119
Taguchi K, Saitoh M, Sato S, et al. Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes. J Pharmacol Exp Ther 1997; 280: 1–5
Michel MC, Grubbel B, Taguchi K, et al. Drugs for treatment of benign pro-static hyperplasia: affinity comparison at cloned α1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol 1996; 16: 21–8
Nickel JC, Sander S, Moon TD. A meta-analysis of the vascular-related safety profile and efficacy of a-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 2008; 62: 1547–59
Guimaraes S, Moura D. Vascular adrenoceptors: an update. Pharmacol Rev 2001; 53: 319–56
Rudner XL, Berkowitz BA, Booth JV, et al. Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and age. Circulation 1999; 100: 2336–43
van Dijk MM, de la Rosette JJMCH, Michel MC. Tamsulosin-modified-release and oral-controlled absorption system formulation in the treatment of benign prostatic hyperplasia. Therapy 2006; 3: 237–46
Tsunoo M, Shishito A, Soeishi Y, et al. Phase I clinical trial of YM617, a new α1 adrenoceptor antagonist: second report. A single oral dose of controlled release formulation in healthy male subjects. Rinsho Iyaku 1990; 6: 2529–51
Tsunoo M, Shishito A, Soeishi Y, et al. Phase I clinical trial of YM617, a new α1 adrenoceptor antagonist: third report. Multiple oral doses of controlled release formulation in healthy male subjects. Rinsho Iyaku 1991; 7: 63–93
Michel MC, Korstanje C, Krauwinkel W, et al. The pharmacokinetic profile of tamsulosin oral controlled absorption system (OCASR). European Urology Supplements 2005; 4(2): 15–24
Michel MC, Korstanje C, Krauwinkel W, et al. Comparison of vascular α1-adrenoceptor antagonism of tamsulosin oral controlled absorption system (OCAS) and modified release (MR) formulations. European Urology Supplements 2005; 4(2): 45–52
Michel MC, Korstanje C, Krauwinkel W, et al. Cardiovascular safety of the oral controlled absorption system (OCAS) formulation of tamsulosin compared to the modified release (MR) formulation. European Urology Supplements 2005; 4(2): 53–60
Tsunoo M, Shishito A, Soeishi Y, et al. Phase I clinical trial of YM617, anew α 1 adrenoceptor antagonist: first report. A single oral dose of conventional formulation in healthy male subjects. Rinsho Iyaku 1990; 6: 2503–28
Matsushima H, Kamimura H, Soeishi Y, et al. Pharmacokinetics and plasma protein binding of tamsulosin hydrochloride in rats, dogs and humans. Drug Metab Dispos 1998; 26: 240–5
Yokoyama O, Takada A, Matsuhima H, et al. Bioequivalence study for tamsulosin hydrochloride 0.2mg oral disintegrating tablets (WOWTAB) and 0.2 mg capsules in humans under the fed condition. Jpn Pharmacol Ther 2005; 33: 521–6
Yokoyama O, Takada A, Matsushima H, et al. Bioequivalence study for tamsulosin hydrochloride 0.2mg oral disintegrating tablets (WOWTAB) and 0.2mg capsules in humans under the fasted condition. Jpn Pharmacol Ther 2005; 33: 527–33
Yokoyama O, Takada A, Matsushima H, et al. Bioequivalence study for tamsulosin hydrochloride 0.2mg and 0.1 mg oral disintegrating tablets (WOWTAB) in humans. Jpn Pharmacol Ther 2005; 33: 535–40
Elias-Al-Mamun M, Khan HA, Dewan I, et al. In vitro study on tamsulosin release kinetics from biodegradable PLGA in situ implants. Pak J Pharm Sci 2009; 22: 360–7
Matsushima H, Kamimura H, Soeishi Y, et al. Plasma protein binding of tamsulosin hydrochloride in renal disease: role of α1-acid glycoprotein and possibility of binding interactions. Eur J Clin Pharmacol 1999; 55: 437–43
Soeishi Y, Kobori M, Kobayashi S, et al. Sensitive method for the determination of amsulosin in human plasma using high-performance liquid chromatography with fluorescence detection. J Chromatography B 1990; 533: 291–6
Ding L, Li L, Tao P, et al. Quantitation of tamsulosin in human plasma by liquid chromatography-electroscopy ionization mass spectrometry. J Chromatography B 2002; 767: 75–81
Qi M, Wang P, Liu L. Determination of tamsulosin in dog plasma by liquid chromatography with atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatography B 2004; 805: 7–11
Soeishi Y, Kobori M, Kobayashi S, et al. Absorption, distribution and excretion of 14C-amsulosin hydrochloride in rats and dogs. Pharmacometrics 1990; 40: 101–9
Witte DG, Brune ME, Katwala SP, et al. Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with a 1-adrenoceptor antagonists. J Pharmacol Exp Ther 2002; 300: 495–504
van Hoogdalem EJ, Soeishi Y, Matsushima H, et al. Disposition of the selective α1A-adrenoceptor antagonist tamsulosin in humans: comparison with data from interspecies scaling. J Pharm Sci 1997; 86: 1156–61
Taguchi K, Schafers RF, Michel MC. Radioreceptor assay analysis of tamsulosin and terazosin pharmacokinetics. Br J Clin Pharmacol 1998; 45: 49–55
Miyazawa Y, Blum RA, Schentag JJ, et al. Pharmacokinetics and safety of tamsulosin in subjects with normal and impaired renal or hepatic function. Curr Ther Res 2001; 62: 603–21
Miyazawa Y, Forrest A, Schentag JJ, et al. Effect of concomitant administration of cimetidine hydrochloride on the pharmacokinetic and safety profile of tamsulosin hydrochloride 0.4 mg in healthy subjects. Curr Ther Res 2002; 63: 15–26
Wolzt M, Fabrizii V, Dorner GT, et al. Pharmacokinetics of tamsulosin in subjects with normal and varying degrees of impaired renal function: an open-label single-dose and multiple-dose study. Eur J Clin Pharmacol 1998; 54: 367–73
Michel MC, Chapple CR. Comparison of the cardiovascular effects of tamsulosin oral controlled absorption system (OCAS®) and alfuzosin prolonged release (XL). Eur Urol 2006; 49: 501–9
Stevens HNE, Speakman M. Behaviour and transit of tamsulosin oral controlled absorption system in the gastrointestinal tract. Curr Med Res Opin 2006; 22: 2323–8
Flomax® (tamsulosin hydrochloride capsules): US prescribing information. Deerfield (IL): Astellas Pharma US, Inc., 2009 Dec [online]. Available from: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Flomax+Caps/Flomax.pdf [Accessed 2009 Dec 14]
Djavan B, Milani S, Davies J, et al. The impact of tamsulosin oral controlled absorption system (OCAS) on nocturia and the quality of sleep: preliminary results of a pilot study. European Urology Supplements 2005; 4(2): 61–8
Yamada S, Ohkura T, Deguchi Y, et al. In vivo measurement by [3H]tamsu-losin of α1 adrenoceptors in rat tissues in relation to the pharmacokinetics. J Pharmacol Exp Ther 1999; 289: 1575–83
Sato S, Ohtake A, Matsushima H, et al. Pharmacological effect of tamsulosin in relation to dog plasma and tissue concentrations: prostatic and urethral retention possibly contributes to uroselectivity of tamsulosin. J Pharmacol Exp Ther 2001; 296: 697–703
Romic I, Kiss T, Kisbenedek L, et al. Tamsulosin drug ratio in prostate versus free fraction in plasma supports pharmacokinetic (PK) contribution to its uroselectivity. J Urol 2003; 169 Suppl.: 288
Matushima H, Watanabe T, Higuchi S. Effect of a 1-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil. J Pharm Sci 2000; 89: 490–8
Koiso K, Akaza H, Kikuchi K, et al. Pharmacokinetics of tamsulosin hydrochloride in patients with renal impairments: effect of α1-acid glycoprotein. J Clin Pharmacol 1996; 36: 1029–38
Soeishi Y, Matsushima H, Teraya Y, et al. Metabolism of tamsulosin in the rat and dog. Xenobiotica 1996; 26: 355–65
Soeishi Y, Matsushima H, Watanabe T, et al. Absorption, metabolism and excretion of tamsulosin hydrochloride in man. Xenobiotica 1996; 26: 637–45
Kamimura H, Oishi S, Matsushima H, et al. Identification of cytochrome P450 isozymes involved in metabolism of the a 1-adrenoceptor blocker tamsulosin in human liver microsomes. Xenobiotica 1998; 28: 909–22
Robinson D, Cardozo L, Terpstra G, et al. A randomized double-blind placebo-controlled multicentre study to explore the efficacy and safety of tamsulosin and tolterodine in women with overactive bladder syndrome. BJU Int 2007; 100: 840–5
Michel MC, de la Rosette JJMCH. a-Blocker treatment of urolithiasis. Eur Urol 2006; 50: 213–4
Michel MC, Mehlburger L, Bressel H-U, et al. Tamsulosin treatment of 19 365 patients with lower urinary tract symptoms: does comorbidity alter tolerability? J Urol 1998; 160: 784–91
Miyazawa Y, Starkey LP, Forrest A, et al. Effects of concomitant administration of tamsulosin (0.8mg/day) on the pharmacokinetic and safety profile of theophylline (5mg/kg): a placebo-controlled evaluation. J Int Med Res 2002; 30: 34–43
Rolan P, Clarke C, Mullins F, et al. Assessment of potential effects of tamsulosin (Omnic®) on the pharmacokinetics and pharmacodynamics of nicoumalone: are there interactions between tamsulosin (Omnis®) and nicoumalone? [abstract]. J Urol 1999; 161 Suppl.: 235
Rolan P, Terpstra IJ, Clarke C, et al. A placebo-controlled pharmacodynamic and pharmacokinetic interaction study between tamsulosin and acenocoumarol. Br J Clin Pharmacol 2003; 55: 314–6
Kang HE, Bae SK, Yoo M, et al. Interaction between udenafil and tamsulosin in rats: non-competitive inhibition of tamsulosin metabolism by udenafil via hepatic CYP3A1/2. Br J Pharmacol 2009; 156: 1009–18
Miyazawa Y, Starkey LP, Forrest A, et al. Effects of concomitant administration of tamsulosin (0.8mg) on the pharmacokinetic and safety profile of intravenous digoxin (Lanoxin®) in normal healthy subjects: a placebo-controlled evaluation. J Clin Pharm Ther 2002; 27: 13–9
Suzuki K, Kawai M, Kaneko N, et al. Study of interactions among colestimide and drugs (2nd report): comparison with cholestyramine. Jpn Pharmacol Ther 2001; 29: 37–44
Troost J, Tatami S, Tsuda Y, et al. Effects of the CYP3A4 inhibitor ketoconazole on the pharmacokinetics of a single oral dose of tamsulosin. Br J Clin Pharmacol. In press
Troost J, Tatami S, Tsuda Y, et al. Effects of the CYP2D6 inhibitor paroxetine on the pharmacokinetics of a single oral dose of tamsulosin. Br J Clin Pharmacol. In press
Modi NB, Kell S, Aquilina J, et al. Effect of dapoxetine on the pharmacokinetics and hemodynamic effects of tamsulosin in men on a stable dose of tamsulosin. J Clin Pharmacol 2008; 48: 1438–50
Abrams P, Speakman M, Stott M, et al. A dose-ranging study of the efficacy and safety of tamsulosin, the first prostate-selective α1A-adrenoceptor antagonist, in patients with benign prostatic obstruction (symptomatic benign prostatic hyperplasia). Br J Urol 1997; 80: 587–96
Lepor H. Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Urology 1998; 51: 892–900
Narayan P, Tewari A, Members of United States 93-01 Study Group. A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. J Urol 1998; 160: 1701–6
Chapple CR, Al-Shukri SH, Gattegno B, et al. Tamsulosin oral controlled absorption system (OCAS) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): efficacy and tolerability in a placebo and active comparator controlled phase 3a study. European Urology Supplements 2005; 4(2): 33–44
Michel MC, Korstanje C, Krauwinkel W. Cardiovascular safety of tamsulosin modified release in the fasted and fed state in elderly healthy subjects. European Urology Supplements 2005; 4(2): 9–14
Djavan B, Chapple C, Milani S, et al. State of the art on the efficacy and tolerability of alpha1-adrenoceptor antagonists in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Urology 2004; 64: 1081–8
Lowe FC. Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect. Clin Ther 1997; 19: 730–42
Michel MC, Bressel H-U, Goepel M, et al. A 6-month large-scale study into the safety of tamsulosin. Br J Clin Pharmacol 2001; 51: 609–14
Michel MC, Neumann HG, Mehlburger L, et al. Does time of administration (morning vs evening) affect the tolerability or efficacy of tamsulosin? BJU Int 2001; 87: 31–4
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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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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DOI: https://doi.org/10.2165/11317580-000000000-00000