Sign Out
Effects on Humans: In a receptor binding assay using human prostate specimen, this product was 2.2 times and 40 times stronger than prazosin hydrochloride and phentolamine mesylate in α1-receptor blocking activity, respectively (in vitro study).
Effects on Animals: Blockade of α-adrenergic receptors: In a receptor binding assay using rat cerebral membrane specimen and an extraction experiment using rabbit aorta specimen, this product inhibited α1-receptors selectively and competitively. Its action was 1/2.2 to 22 times more potent than prazosin hydrochloride and 45 to 140 times more potent than phentolamine mesylate. In extraction experiments using isolated rabbit aorta, isolated rat vas deferens and isolated guinea pig intestine specimen, tamsulosin hydrochloride proved to be 5,400 to 24,000 times more selective for α1-receptors than for α2-receptors (in vitro study).
Effect on the lower urinary tract (urethra and urinary bladder) and prostate: In an extraction experiment using smooth muscle from rabbit urethra, prostate and urinary bladder base specimen, tamsulosin hydrochloride was 23 to 98 times more potent than prazosin hydrochloride in α1-receptor blocking activity, and 87 to 320 times more potent than phentolamine mesylate (in vitro study).
In anesthetized dogs, the drug inhibited the α1-agonist (phenylephrine)-induced increase in intrauretheral pressure with 13 times greater potency than the increase in diastolic blood pressure.
Improvement of bladder outlet obstruction: In anesthetized male dogs, this product decreased urethral pressure in the prostatic zone of the intraurethral pressure curve. In anesthetized rats, however, the drug did not affect rhythmic bladder contraction or threshold intravesical pressure.
Clinical Studies: Clinical Studies for Efficacy and Safety: Phase II/III study in Japan: This product significantly decreased intraurethral pressure in the prostatic urethra, and improved urinary flow rate and residual urine volume in a dose-dependent manner. The evaluation results of overall improvement in 276 cases are presented in the following table. Results of a double-blind comparative study showed that HARNAL Capsules administered in a 0.2 mg once daily dose was clinically useful. (See Table 1.)
Click on icon to see table/diagram/imagePharmacokinetics: Blood Level: Single dose: The plasma concentration of unchanged drug reached its peak 7 to 8h after an oral administration of 0.1 to 0.6mgNote) HARNAL Capsules to healthy adults. The half-life was 9.0 to 11.6h. The Cmax and AUC increased in a nearly dose-dependent manner. In a 7-day repeated oral administration study, the half-life was slightly prolonged and plasma concentrations reached a steady state on day 4. (See Table 2.)
Click on icon to see table/diagram/imageBioequivalence study: When a single dose of HARNAL D Tablets 0.2mg or HARNAL 0.2mg Capsules is orally administered to healthy adults using a cross-over method, the plasma concentration of unchanged tamsulosin hydrochloride is shown as follows. HARNAL D Tablets and HARNAL Capsules were demonstrated to be bioequivalent. (See figure and Table 3.)
Click on icon to see table/diagram/image
Click on icon to see table/diagram/imageMetabolism: In vitro experiments show Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.
Drug Interaction: PK studies in healthy volunteers revealed that concomitant administration with strong inhibitors of CYP3A4 or CYP2D6 may lead to increased exposure to tamsulosin. Concomitant administration with ketoconazole (a known CYP3A4 inhibitor) resulted in a Cmax and AUC of tamsulosin that had increased by a factor of 2.2 and 2.8, respectively. Concomitant administration with paroxetine (a known CYP2D6 inhibitor) resulted in a Cmax and AUC of tamsulosin that had increased by a factor of 1.3 and 1.6, respectively.
Excretion: HARNAL Capsules of 0.1 to 0.6mgNote) were orally administered to healthy adults. The excretion rate of the unchanged drug in the urine up to 30h after administration remained almost constant at 12% to 14%. No significant changes in the excretion rate after repeated administrations were observed.
Patients with Specific Backgrounds: Patients with renal impairment: HARNAL 0.2mg Capsules were orally administered to 11 patients with renal dysfunction. Their blood pressure did not decrease, but an increase in the plasma concentration of tamsulosin hydrochloride was observed in 2 patients with serious renal impairment. The plasma concentrations of the drug were intimately correlated with an increase in the plasma concentration of α1-AGP (α1-acid glycoprotein).
This increase in the plasma concentration of the drug may be caused by the binding of the tamsulosin hydrochloride to plasma α1-AGP. [See Precautions Concerning Patients with Specific Backgrounds: Patients with Renal Impairment: Patients with severe renal impairment and Use in the Elderly under Precautions.]
In addition, the plasma concentration of the unbound drug, which is presumed to be directly related to the appearance of the effects and adverse reactions of tamsulosin hydrochloride, was almost the same for these patients as for persons with normal renal function, regardless of the plasma concentration of α1-AGP.
Note) The approved daily dose for this product is 0.2mg. The dosage may be adjusted depending on the patient's age and symptoms.
