Distribution: The mean steady-state apparent volume of distribution of tamsulosin HCI after intravenous administration to ten healthy male adults was 16L, which is suggestive of distribution into extracellular fluids in the body. Additionally, whole body autoradiographic studies in mice and rats and tissue distribution in rats and dogs indicate that tamsulosin HCI is widely distributed to most tissues including kidney, prostate, liver, gall bladder, heart, aorta, and brown fat, and minimally distributed to the brain, spinal cord, and testes. Tamsulosin HCI is extensively bound to human plasma proteins (94% to 99%), primarily alpha-1 acid glycoprotein (AAG), with linear binding over a wide concentration range (20 to 600 ng/ mL). The results of two-way in vitro studies indicate that the binding of tamsulosin HCI to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, tamsulosin HCI had no effect on the extent of binding of these drugs. Metabolism: There is no enantiomeric bioconversion from tamsulosin HCI [R(-) isomer] to the S(+) isomer in humans. Tamsulosin HCI is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. However, the pharmacokinetic profile of the metabolites in humans has not been established. Additionally, the cytochrome P450 enzymes that primarily catalyze the Phase I metabolism of tamsulosin HCI have not been conclusively identified. Therefore, possible interactions with other cytochrome P450 metabolized compounds cannot be discerned with current information. The metabolites of tamsulosin HCI undergo extensive conjugation to glucuronide or sulfate prior to renal excretion. | ||||
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