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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. Text Continues Below
Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between tamsulosin HCI and amitriptyline, albuterol (beta agonist), glyburide (glibenclamide) and finasteride (5alpha-reductase inhibitor for treatment of BPH). However, results of the in vitro testing of the tamsulosin HCI interaction with diclofenac and warfarin were equivocal. Excretion: On administration of the radiolabeled dose of tamsulosin HCI to four healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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