(Figure 1).

Figure 1: Mean Plasma Tamsulosin HCI Concentrations Following Single-Dose Administration of FLOMAX capsules 0.4 mg Under Fasted and Fed

Conditions (n= 8)

The effects of food on the pharmacokinetics of tamsulosin HCI are consistent regardless of whether a FLOMAX capsule is taken with a light breakfast or a high-fat breakfast (Table 1).

TABLE 1 Mean (± S. D.) Pharmacokinetic Parameters Following FLOMAX capsules 0.4 mg Once Daily or 0.8 mg Once Daily with a Light Breakfast, High-Fat

Breakfast or Fasted Pharmacokinetic

Parameter 0. 4 mg q. d. to healthy volunteers; n= 33 (age range 18-32 years) 0.8 mg q. d. to healthy volunteers; n= 22 (age range 55-75 years) Light Breakfast Fasted Light Breakfast High-Fat Breakfast Fasted

Cmin (ng/ mL) 4.0 ± 2.6 3.8 ± 2.5 12.3 ± 6.7 13.5 ± 7.6 13.3 ± 13. 3 Cmax (ng/ mL)

10.1 ± 4.8 17.1 ± 17. 1 29.8 ± 10. 3 29.1 ± 11. 0 41.6 ± 15. 6 Cmax/ Cmin Ratio 3.1 ± 1.0 5.3 ± 2.2 2.7 ± 0.7 2.5 ± 0.8 3.6 ± 1.1

Tmax (hours) 6.0 4.0 7.0 6.6 5.0 T1/ 2 (hours) ----14.9 ± 3.9

AUC . (ng . hr/ mL) 151 ± 81. 5 199 ± 94. 1 440 ± 195 449 ± 217 557 ± 257 Cmin = observed minimum concentration

Cmax = observed maximum tamsulosin HCI plasma concentration Tmax = median time-to-maximum concentration

T1/ 2 = observed half-life AUC . = Area under the tamsulosin HCI plasma time curve over the dosing interval

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.