Tamsulosin pharmacokinetics and molecular data: Difference between revisions
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== | ==Pharmacokinetics== | ||
<font size="4">[[Tamsulosin pharmacokinetics and molecular data#Absorption|Absorption]]</font> | <font size="4">[[Tamsulosin pharmacokinetics and molecular data#Absorption|Absorption]]</font> | ||
<br> | <br> | ||
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===Absorption=== | ===Absorption=== | ||
Absorption of tamsulosin HCl from | Absorption of tamsulosin HCl from Tamsulosin capsules 0.4 mg is essentially complete | ||
(>90%) following oral administration under fasting conditions. Tamsulosin HCl exhibits | (>90%) following oral administration under fasting conditions. Tamsulosin HCl exhibits | ||
linear kinetics following single and multiple dosing, with achievement of steady-state | linear kinetics following single and multiple dosing, with achievement of steady-state | ||
concentrations by the fifth day of once-a-day dosing. | concentrations by the fifth day of once-a-day dosing. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Effect of Food=== | ===Effect of Food=== | ||
The time to maximum concentration (Tmax) is reached by four to five hours under fasting | The time to maximum concentration (Tmax) is reached by four to five hours under fasting | ||
conditions and by six to seven hours when | conditions and by six to seven hours when Tamsulosin capsules are administered with food. | ||
Taking | 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 | bioavailability (AUC) and 40% to 70% increase in peak concentrations (Cmax) compared to | ||
fed conditions. | fed conditions. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Distribution=== | ===Distribution=== | ||
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and rats and tissue distribution in rats and dogs indicate that tamsulosin HCl is widely | 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 | 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. | brown fat, and minimally distributed to the brain, spinal cord, and testes. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Metabolism=== | ===Metabolism=== | ||
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with other cytochrome P450 metabolized compounds cannot be discerned with current | with other cytochrome P450 metabolized compounds cannot be discerned with current | ||
information. The metabolites of tamsulosin HCl undergo extensive conjugation to | information. The metabolites of tamsulosin HCl undergo extensive conjugation to | ||
glucuronide or sulfate prior to renal excretion. | glucuronide or sulfate prior to renal excretion. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Excretion=== | ===Excretion=== | ||
On administration of the radiolabeled dose of tamsulosin HCl to four healthy volunteers, 97% | 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 | of the administered radioactivity was recovered, with urine (76%) representing the primary | ||
route of excretion compared to feces (21%) over 168 hours. | route of excretion compared to feces (21%) over 168 hours. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Geriatrics (Age)=== | ===Geriatrics (Age)=== | ||
Cross-study comparison of | 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 | 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 | 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 | 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. | exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Renal Dysfunction=== | ===Renal Dysfunction=== | ||
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clearance, remained relatively constant. Therefore, patients with renal impairment do not | clearance, remained relatively constant. Therefore, patients with renal impairment do not | ||
require an adjustment in FLOMAX capsules dosing. However, patients with endstage renal | require an adjustment in FLOMAX capsules dosing. However, patients with endstage renal | ||
disease (CLcr <10 mL/min/1.73m2) have not been studied. | disease (CLcr <10 mL/min/1.73m2) have not been studied. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
===Hepatic Dysfunction=== | ===Hepatic Dysfunction=== | ||
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not change significantly with only a modest (32%) change in intrinsic clearance of unbound | 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 | tamsulosin HCl. Therefore, patients with moderate hepatic dysfunction do not require an | ||
adjustment in | adjustment in Tamsulosin capsules dosage. ''[[Tamsulosin pharmacokinetics and molecular data#Pharmacokinetics|Return to top]]'' | ||
<br> | <br> | ||
<br> | <br> |
Latest revision as of 17:37, 20 December 2011
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
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
Adapted from the FDA Package Insert.