Tamsulosin pharmacokinetics and molecular data

# Pharmacokinetics
Absorption
Effect of Food
Distribution
Metabolismr
Excretion
Geriatrics (Age)
Renal Dysfunction
Hepatic Dysfunction

## Absorption
Absorption of tamsulosin HCl from Tamsulosin capsules 0.4 mg is essentially complete
(>90%) following oral administration under fasting conditions. Tamsulosin HCl exhibits
linear kinetics following single and multiple dosing, with achievement of steady-state
concentrations by the fifth day of once-a-day dosing. Return to top

## Effect of Food
The time to maximum concentration (Tmax) is reached by four to five hours under fasting
conditions and by six to seven hours when Tamsulosin capsules are administered with food.
Taking Tamsulosin capsules under fasted conditions results in a 30% increase in
bioavailability (AUC) and 40% to 70% increase in peak concentrations (Cmax) compared to
fed conditions. Return to top

## Distribution
The mean steady-state apparent volume of distribution of tamsulosin HCl 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 HCl 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. Return to top

## Metabolism
There is no enantiomeric bioconversion from tamsulosin HCl  to the S(+)
isomer in humans. Tamsulosin HCl 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
-f tamsulosin HCl have not been conclusively identified. Therefore, possible interactions
with other cytochrome P450 metabolized compounds cannot be discerned with current
information. The metabolites of tamsulosin HCl undergo extensive conjugation to
glucuronide or sulfate prior to renal excretion. Return to top

## Excretion
On administration of the radiolabeled dose of tamsulosin HCl to four healthy volunteers, 97%
-f the administered radioactivity was recovered, with urine (76%) representing the primary
route of excretion compared to feces (21%) over 168 hours. Return to top

## Geriatrics (Age)
Cross-study comparison of Tamsulosin capsules overall exposure (AUC) and half-life indicate
that the pharmacokinetic disposition of tamsulosin HCl may be slightly prolonged in geriatric
males compared to young, healthy male volunteers. Intrinsic clearance is independent of
tamsulosin HCl binding to AAG, but diminishes with age, resulting in a 40% overall higher
exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years. Return to top

## Renal Dysfunction
The pharmacokinetics of tamsulosin HCl have been compared in 6 subjects with mildmoderate
(30CLcr <70 mL/min/1.73m2) or moderate-severe (10CLcr <30 mL/min/1.73m2)
renal impairment and 6 normal subjects (CLcr <90 mL/min/1.73m2). While a change in the
-verall plasma concentration of tamsulosin HCl was observed as the result of altered binding
to AAG, the unbound (active) concentration of tamsulosin HCl, as well as the intrinsic
clearance, remained relatively constant. Therefore, patients with renal impairment do not
require an adjustment in FLOMAX capsules dosing. However, patients with endstage renal
disease (CLcr <10 mL/min/1.73m2) have not been studied. Return to top

## Hepatic Dysfunction
The pharmacokinetics of tamsulosin HCl have been compared in 8 subjects with moderate
hepatic dysfunction (Child-Pughs classification: Grades A and B) and 8 normal subjects.
While a change in the overall plasma concentration of tamsulosin HCl was observed as the
result of altered binding to AAG, the unbound (active) concentration of tamsulosin HCl does
not change significantly with only a modest (32%) change in intrinsic clearance of unbound
tamsulosin HCl. Therefore, patients with moderate hepatic dysfunction do not require an
adjustment in Tamsulosin capsules dosage. Return to top
Adapted from the FDA Package Insert.