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Combination therapy with dutasteride and tamsulosin for the treatment of symptomatic enlarged prostate.

Miller J, Tarter TH - Clin Interv Aging (2009)

Bottom Line: Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist.Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility.Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5alpha-reductase inhibitor dutasteride and the alpha1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone.

View Article: PubMed Central - PubMed

Affiliation: Southern Illinois University School of Medicine, Department of Surgery, Springfield, IL 62794-9665, USA.

ABSTRACT
Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist. Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that alpha1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5alpha-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5alpha-reductase inhibitor dutasteride and the alpha1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone.

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Dutasteride chemical structure.
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f1-cia-4-251: Dutasteride chemical structure.

Mentions: Dutasteride is in a drug class known as 17β-substituted 4-aza-steroids with the chemical name (5α, 17β)-N {2, 5, bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide. The structural formula is shown in Figure 1. It is a competitive inhibitor of type 1 and type 2 5α-reductase isoenzymes. It forms a stable complex with a slow rate of dissociation, and does not bind the androgen receptor. The bioavailability of dutasteride is approximately 60% and peak serum concentration is achieved after 2 to 3 hours. The time to steady state is dose dependent, and at a dose of 0.5 mg/day is approximately 3 months. More than 99.5% of circulating dutasteride is bound to plasma proteins, and has a volume of distribution of 300 to 500 L. Clearance is linear at 0.58 L/hour, resulting in a half-life of up to 5 weeks. Pharmacokinetic data are summarized in Table 1. Dutasteride is detectable (greater than 0.1 ng/mL) in the serum 4 to 6 months after discontinuation of treatment. The drug is extensively metabolized by cytochrome-P3A4 in the liver and is excreted mainly in the feces. Only trace amounts are excreted in the urine. Following dosing to steady state, 5 major metabolites are detectable in the serum. The major metabolite, 6β-hydroxydutasteride, has pharmacological activity comparable to dutasteride.9


Combination therapy with dutasteride and tamsulosin for the treatment of symptomatic enlarged prostate.

Miller J, Tarter TH - Clin Interv Aging (2009)

Dutasteride chemical structure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2697590&req=5

f1-cia-4-251: Dutasteride chemical structure.
Mentions: Dutasteride is in a drug class known as 17β-substituted 4-aza-steroids with the chemical name (5α, 17β)-N {2, 5, bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide. The structural formula is shown in Figure 1. It is a competitive inhibitor of type 1 and type 2 5α-reductase isoenzymes. It forms a stable complex with a slow rate of dissociation, and does not bind the androgen receptor. The bioavailability of dutasteride is approximately 60% and peak serum concentration is achieved after 2 to 3 hours. The time to steady state is dose dependent, and at a dose of 0.5 mg/day is approximately 3 months. More than 99.5% of circulating dutasteride is bound to plasma proteins, and has a volume of distribution of 300 to 500 L. Clearance is linear at 0.58 L/hour, resulting in a half-life of up to 5 weeks. Pharmacokinetic data are summarized in Table 1. Dutasteride is detectable (greater than 0.1 ng/mL) in the serum 4 to 6 months after discontinuation of treatment. The drug is extensively metabolized by cytochrome-P3A4 in the liver and is excreted mainly in the feces. Only trace amounts are excreted in the urine. Following dosing to steady state, 5 major metabolites are detectable in the serum. The major metabolite, 6β-hydroxydutasteride, has pharmacological activity comparable to dutasteride.9

Bottom Line: Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist.Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility.Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5alpha-reductase inhibitor dutasteride and the alpha1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone.

View Article: PubMed Central - PubMed

Affiliation: Southern Illinois University School of Medicine, Department of Surgery, Springfield, IL 62794-9665, USA.

ABSTRACT
Benign prostatic hyperplasia (BPH) is a frequent cause of lower urinary symptoms, with a prevalence of 50% by the sixth decade of life. Hyperplasia of stromal and epithelial prostatic elements that surround the urethra cause lower urinary tract symptoms (LUTS), urinary tract infection and acute urinary retention. Medical treatments of symptomatic BPH include; 1) the 5alpha-reductase inhibitors, 2) the alpha1-adrenergic antagonists, and 3) the combination of a 5alpha-reductase inhibitor and a alpha1-adrenergic antagonist. Selective alpha1-adrenergic antagonists relax the smooth muscle of the prostate and bladder neck without affecting the detrussor muscle of the bladder wall, thus decreasing the resistance to urine flow without compromising bladder contractility. Clinical trials have shown that alpha1-adrenergic antagonists decrease LUTS and increase urinary flow rates in men with symptomatic BPH, but do not reduce the long-term risk of urinary retention or need for surgical intervention. Inhibitors of 5alpha-reductase decrease production of dihydrotestosterone within the prostate resulting in decreased prostate volumes, increased peak urinary flow rates, improvement of symptoms, and decreased risk of acute urinary retention and need for surgical intervention. Interim results of the ongoing Combination of Avodart and Tamsulosin (CombAt) study have shown combination therapy with the 5alpha-reductase inhibitor dutasteride and the alpha1-adrenergic antagonist tamsulosin offer significant improvements from baseline compared with either drug alone.

Show MeSH
Related in: MedlinePlus