Tamsulosin pharmacokinetics and molecular data

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pharmacokinetics

Absorption

Effect of Food

Distribution

Metabolismr

Excretion

Geriatrics (Age)

Renal Dysfunction

Hepatic Dysfunction

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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 [R(-) isomer] 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 of 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% of 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 (30≤CLcr <70 mL/min/1.73m2) or moderate-severe (10≤CLcr <30 mL/min/1.73m2) renal impairment and 6 normal subjects (CLcr <90 mL/min/1.73m2). 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, 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-Pugh’s 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

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Adapted from the FDA Package Insert.