Urilax Mechanism of Action

Pharmacology: Pharmacokinetics: EC tablet: Tamsulosin is absorbed from the gastrointestinal tract and is almost completely bioavailable. The extent and rate of absorption are reduced in the presence of food. Following oral administration of an immediate release preparation, peak plasma concentrations occur about 1 hour after a dose. Tamsulosin is metabolized slowly in the liver and is excreted mainly in the urine as metabolites and some unchanged drug. The plasma elimination half-life has been reported to be between 4 and 5.5 hours. Tamsulosin is about 99% bound to plasma proteins.
Some of the pharmacokinetic value cited above may be altered when tamsulosin is administered as a modified-release preparation, the form in which it is usually employed; for instance, peak plasma concentrations occur about 6 hours after a dose and the apparent elimination half-life may be 10 to 13 hours.
ER tablet: Tamsulosin is a selective alpha-1 antagonist that acts by decreasing the smooth muscle tone in the prostate and urinary bladder neck with resultant increase in the urine flow and relief of the symptoms associated with benign prostatic hyperplasia. Although the symptoms of benign prostatic hyperplasia is mostly due to an increase in the size of the prostate gland with proliferation of smooth muscle cells in the stroma of the prostate, these urinary symptoms are partly due to an increase in smooth muscle tone in the prostate and urinary bladder neck mediated by sympathetic nervous system stimulation of alpha-1 adrenergic receptors. Tamsulosin exhibits selectivity for alpha-1 adrenergic receptors of the A subtype as opposed to the B subtype which is important in maintaining the vascular smooth muscle tone. Since about 70% of the alpha-1 adrenergic receptors found in the human prostate gland are of the subtype alpha-1A, tamsulosin as expected was demonstrated to be efficacious in relieving the symptoms associated with benign prostatic hyperplasia with little or no alteration noted in the baseline systemic blood pressure.
Urilax is formulated as an extended release tablet of the non-ionic gel matrix type. Tamsulosin administered as an extended release tablet is absorbed from the intestine with a bioavailability of approximately 55-59%. The extended release formulation allows slow and consistent release of tamsulosin which is maintained over the whole pH range encountered in the gastrointestinal tract with little fluctuation over 24 hours allowing it to be administered on a once daily dosing. The rate and extent of absorption of orally administered tamsulosin extended release tablet is not affected by oral food intake. Tamsulosin extended release tablets demonstrate linear pharmacokinetics with median time to peak plasma levels (T_max) of 6 hours after a single oral dose given in the fasted state. On day 4 of multiple daily oral dosing when steady state conditions have expectedly been achieved, T_max is 4 to 6 hours irrespective of whether the tamsulosin extended release tablet was orally administered in the fasted or fed state. The peak plasma level (C_max) is approximately 6 ng/mL with the first dose of tamsulosin extended release tablet but increases to 11 ng/mL after achievement of the steady state condition. As a result of the extended release formulation of Urilax, the trough plasma concentration of tamsulosin falls only to 40% of the peak plasma concentration under both fasted and fed states. There is however considerable inter-patient variation in plasma levels of tamsulosin both after single and multiple oral dosing. Based on a bio-equivalent study done on 40 healthy adult Korean males which compared Urilax (Uronal SR in Korea) 200 mcg tablets to Harnal-D 200 mcg tablets, there were no significant difference noted in terms of the maximum serum concentrations (C_max 90% CI log 0.9276 - log 1.0793) and area under the curve (AUC 90% CI log 0.9943 - log 1.2231). Tamsulosin is about 99% bound to plasma proteins with a small volume of distribution of about 0.2 L/kg. Tamsulosin has a low first-pass effect on account of its slow hepatic metabolism.
Most of the orally administered tamsulosin is present in the plasma in the form of unchanged drug though it is extensively metabolized by the cytochrome P450 enzymes in the liver and only about 4-6% of the oral dose is excreted unchanged in the urine. In rats, hardly any induction of microsomal liver enzymes was noted to be caused by the administration of tamsulosin. Orally administered tamsulosin is mostly recovered in the urine both as unchanged drug and as inactive metabolites with only 20% of the oral dose recovered in the feces. All of the metabolites of tamsulosin are either inactive or only slightly active compared to the original compound. The elimination half-life (T_1/2) of Urilax is about 19 hours after a single dose and 15 hours in steady state conditions after multiple oral dosing.