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Triamterene | CAS No: 396-01-0 | GMP-certified suppliers
A medication that treats edema linked to cardiovascular and liver disorders while managing hypertension and maintaining potassium balance in combination therapies.
Therapeutic categories
Primary indications
- Triamterene is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome
- Also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism
- Triamterene in combination with hydrochlorothiazide is indicated for the managment of hypertension or treatment of edema in patients who develop hypokalemia following hydrochlorothiazide monotherapy, and in patients who require thiazide diuretic and in whom the development of hypokalemia cannot be risked
Product Snapshot
- Triamterene is formulated as an oral small molecule available in tablet and capsule forms
- It is primarily used for managing edema associated with congestive heart failure, liver cirrhosis, nephrotic syndrome, and to maintain potassium balance in combination with diuretics for hypertension and edema treatment
- Triamterene is approved for use in major regulatory markets including the United States and Canada
Clinical Overview
Pharmacologically, triamterene acts on the distal nephron segments of the kidney, specifically the late distal convoluted tubule and collecting duct. Its mechanism of action involves inhibition of epithelial sodium channels (ENaC) on the luminal side of tubular cells. By blocking these channels, triamterene reduces sodium reabsorption and consequently decreases potassium and hydrogen ion excretion. This delays sodium uptake without antagonizing aldosterone directly but produces effects antagonistic to mineralocorticoid action. Its natriuretic efficacy is limited due to the small fraction of sodium reabsorbed at its site of action.
Key pharmacodynamic effects include increased renal clearance of sodium and magnesium and reduced clearance of uric acid and creatinine, attributed to a reduction in glomerular filtration and renal plasma flow. Triamterene does not alter calcium excretion. Notably, it increases serum potassium levels, carrying a documented risk of hyperkalemia, which can lead to cardiac arrhythmias. Additionally, it has weak antifolate activity and potential to induce photosensitivity reactions.
Its absorption, metabolism, and elimination parameters include oral bioavailability with renal excretion being significant for the unchanged drug and metabolites, although detailed ADME profiles vary among patients. Triamterene is recognized as both a substrate of cytochrome P-450 CYP1A2 and a membrane transport modulator, underscoring potential drug interaction considerations.
Since its U.S. FDA approval in 1964, triamterene has been widely utilized, often in fixed-dose combinations with hydrochlorothiazide to enhance antihypertensive efficacy while mitigating the hypokalemic risk posed by thiazide diuretics.
For API sourcing and quality assurance, triamterene must meet stringent purity criteria due to its narrow therapeutic index and risk of hyperkalemia. Supply chains should ensure compliance with pharmacopeial standards and regulatory guidelines, with particular attention to polymorphic form, residual solvents, and impurities that could impact bioavailability and safety. Stability during storage and shipment must be validated to maintain potency, as degradation products may pose toxicity concerns.
Identification & chemistry
| Generic name | Triamterene |
|---|---|
| Molecule type | Small molecule |
| CAS | 396-01-0 |
| UNII | WS821Z52LQ |
| DrugBank ID | DB00384 |
Pharmacology
| Summary | Triamterene is a potassium-sparing diuretic that targets amiloride-sensitive epithelial sodium channels (ENaC) in the late distal convoluted tubule and collecting duct of the kidney. By inhibiting sodium reabsorption at these sites, it reduces sodium uptake and decreases potassium excretion, thereby promoting natriuresis with potassium retention. Its action mitigates potassium loss associated with other diuretics and contributes to diuresis and blood pressure modulation without directly antagonizing aldosterone. |
|---|---|
| Mechanism of action | Triamterene inhibits the epithelial sodium channels (ENaC) located on the lumenal side in the late distal convoluted tubule and collecting tubule , which are transmembrane channels that normally promote sodium uptake and potassium secretion. In the late distal tubule to the collecting duct, sodium ions are actively reabsorbed via ENaC on the luminal membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase, with water following passively. Triamterene exerts a diuretic effect on the distal renal tubule to inhibit the reabsorption of sodium ions in exchange for potassium and hydrogen ions and its natriuretic activity is limited by the amount of sodium reaching its site of action. Its action is antagonistic to that of adrenal mineralocorticoids, such as aldosterone, but it is not an inhibitor or antagonist of aldosterone. Triamterene maintains or increases sodium excretion, thereby increasing the excretion of water, and reducing the excess loss of potassium, hydrogen, and chloride ions by inhibiting the distal tubular exchange mechanism. Due to its diuretic effect, triamterene rapidly and reversibly reduces the lumen-negative transepithelial potential difference by almost completely abolishing Na+ conductance without altering K+ conductance. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion. Triamterene is similar in action to [amiloride] but, unlike amiloride, increases the urinary excretion of magnesium. |
| Pharmacodynamics | Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion. As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities. In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine due to its effect of reducing glomerular filtration renal plasma flow. Triamterene does not affect calcium excretion. In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Amiloride-sensitive sodium channel subunit gamma | Humans | inhibitor |
| Amiloride-sensitive sodium channel subunit alpha | Humans | inhibitor |
| Amiloride-sensitive sodium channel subunit beta | Humans | inhibitor |
ADME / PK
| Absorption | Triamterene is shown to be rapidly absorbed in the gastrointestinal tract Its onset of action achiveved within 2 to 4 hours after oral ingestion and its duration of action is 12-16 hours. It is reported that the diuretic effect of triamterene may not be observed for several days after administration. In a pharmacokinetic study, the oral bioavailability of triamterene was determined to be 52%. Following administration of a single oral dose to fasted healthy male volunteers, the mean AUC of triamterene was about 148.7 ng*hr/mL and the mean peak plasma concentrations (Cmax) were 46.4 ng/mL reached at 1.1 hour after administration. In a limited study, administration of triamterene in combination with hydrochlorothiazide resulted in an increased bioavailability of triamterene by about 67% and a delay of up to 2 hours in the absorption of the drug. It is advised that triamterene is administered after meals; in a limited study, combination use of triamterene and hydrochlorothiazide with the consumption of a high-fat meal resulted in an increase in the mean bioavailability and peak serum concentrations of triamterene and its active sulfate metabolite, as well as a delay of up to 2 hours in the absorption of the active constituents. |
|---|---|
| Half-life | The half-life of the drug in plasma ranges from 1.5 to 2 hours. In a pharmacokinetic study involving healthy volunteers, the terminal half-lives for triamterene and 4′-hydroxytriamterene sulfate were 255 ± 42 and 188 ± 70 minutes, respectively, after intravenous infusion of the parent drug. |
| Protein binding | 67% bound to proteins. |
| Metabolism | Triamterene undergoes phase I metabolism involving hydroxylation, via CYP1A2 activity, to form 4'-hydroxytriamterene. 4'-Hydroxytriamterene is further transformed in phase II metabolism mediated by cytosolic sulfotransferases to form the major metabolite, 4′-hydroxytriamterene sulfate, which retains a diuretic activity. Both the plasma and urine levels of this metabolite greatly exceed triamterene levels while the renal clearance of the sulfate conjugate was les than that of triamterene; this low renal clearance of the sulfate conjugate as compared with triamterene may be explained by the low unbound fraction of the metabolite in plasma. |
| Route of elimination | Triamterene and its metabolites are excreted by the kidney by filtration and tubular secretion. Upon oral ingestion, somewhat less than 50% of the oral dose reaches the urine. About 20% of an oral dose appears unchanged in the urine, 70% as the sulphate ester of hydroxytriamterene and 10% as free hydroxytriamterene and triamterene glucuronide. |
| Volume of distribution | In a pharmacolinetic study involving healthy volunteers receiving triamterene intravenously, the volumes of distribution of the central compartment of triamterene and its hydroxylated ester metabolite were 1.49 L/kg and 0.11 L/kg, respectively. Triamterene was found to cross the placental barrier and appear in the cord blood of animals. |
| Clearance | The total plasma clearance was 4.5 l/min and renal plasma clearance was 0.22 l/kg following intravenous administration of triamterene in healthy volunteers. |
Formulation & handling
- Triamterene is a small molecule intended for oral administration in tablet or capsule formulations.
- It has moderate water solubility and low lipophilicity (LogP 1.11), which may influence formulation strategies for dissolution and absorption.
- Formulations should account for potential interactions with potassium-containing foods or supplements due to hyperkalemia risk.
Regulatory status
| Lifecycle | The API’s primary patents have expired in both Canada and the US, allowing for generic entry and widespread availability. The product is currently marketed in these regions with established formulations. |
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| Markets | Canada, US |
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Supply Chain
| Supply chain summary | Triamterene is primarily manufactured by Wellspring Pharmaceutical Corp and supplied through a broad network of packagers and distributors, indicating a well-established manufacturing and supply infrastructure. Branded products such as Dyazide have a strong presence in the US and Canadian markets. The availability of multiple manufacturers and packagers suggests that patent exclusivity has expired, allowing for widespread generic competition. |
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Safety
| Toxicity | Acute oral LD50 of triamterene in rats is 400 mg/kg and 285-380 mg/kg in mice.[L6166,MSDS] There has been a case of reversible acute renal failure following ingestion of 50 combination pills containing 50 mg triamterene and 25 mg hydrochlorothiazide. Symptoms of overdose, such as nausea, vomiting, gastrointestinal disturbances, weakness, and hypotension, are related to electrolyte imbalances, such as hyperkalemia. As there is no specific antidote, emesis and gastric lavage should be use to induce immediate evacuation of the stomach and careful evaluation of the electrolyte pattern and fluid balance should be made. Dialysis may be somewhat effective in case of an overdosage. In a carciongenicity study in male and female mice administered with triamterene at the highst dosage level, there was an increased incidence of hepatocellular neoplasia, primarily adenomas. However, this was not a dose-dependent phenomenon and there was no statistically significant difference from control incidence at any dose level. In bacterial assays, there was no demonstrated mutagenic potential of triamterene. In in vitro assay using Chinese hamster ovary (CHO) cells with or without metabolic activation, there were no chromosomal aberrations. Studies evaluating the effects of triamterene on reproductive system or fertility have not been conducted. It is advised that the use of triamterene is avoided during pregnancy. As triamterene has been detected in human breast milk, triamterene should be used when nursing is ceased. |
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- Triamterene exhibits moderate acute oral toxicity with LD50 values of 285-400 mg/kg in rodents
- Overdose may cause electrolyte imbalances such as hyperkalemia
- Carcinogenicity studies showed a non-dose-dependent increase in hepatocellular adenomas in mice, with no mutagenic or chromosomal aberration effects observed in vitro
Triamterene is a type of Diuretics
Diuretics, a subcategory of pharmaceutical active pharmaceutical ingredients (APIs), are compounds commonly used in the treatment of conditions such as hypertension, congestive heart failure, and edema. Diuretics, also known as water pills, function by increasing the production of urine, thereby promoting the excretion of excess water and electrolytes from the body.
There are several types of diuretics, including thiazide diuretics, loop diuretics, and potassium-sparing diuretics. Thiazide diuretics, such as hydrochlorothiazide, work by inhibiting the reabsorption of sodium and chloride in the kidneys, leading to increased urine production. Loop diuretics, such as furosemide, act on the loop of Henle in the kidneys to block the reabsorption of sodium and chloride, resulting in a more potent diuretic effect. Potassium-sparing diuretics, like spironolactone, help retain potassium in the body while still promoting diuresis.
These diuretic APIs are widely used in the pharmaceutical industry to formulate medications that effectively manage fluid retention and related conditions. They are available in various forms, including tablets, capsules, and intravenous formulations. Diuretics are often prescribed as part of combination therapies to enhance their effectiveness and minimize adverse effects.
It is important to note that the use of diuretics should be closely monitored by healthcare professionals due to potential side effects such as electrolyte imbalances, dehydration, and hypotension. Proper dosage and patient-specific considerations are crucial to ensure optimal therapeutic outcomes.
In conclusion, diuretics are a vital subcategory of pharmaceutical APIs used to treat conditions characterized by fluid retention. Their mechanisms of action vary, but they all facilitate increased urine production, assisting the body in eliminating excess fluids. The proper use of diuretics, in combination with medical supervision, can effectively manage various cardiovascular and renal conditions.
Triamterene (Diuretics), classified under Antihypertensive agents
Antihypertensive agents are a crucial category of pharmaceutical active pharmaceutical ingredients (APIs) used to treat high blood pressure, also known as hypertension. These medications are designed to lower blood pressure and reduce the risk of associated cardiovascular complications.
Antihypertensive agents function by targeting various mechanisms involved in blood pressure regulation. Some common classes of antihypertensive agents include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers (CCBs), and diuretics.
ACE inhibitors work by inhibiting the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that constricts blood vessels. ARBs, on the other hand, block the receptors to which angiotensin II binds, thereby preventing its vasoconstrictive effects.
Beta-blockers reduce blood pressure by blocking the effects of adrenaline and noradrenaline, which are responsible for increasing heart rate and constricting blood vessels. CCBs inhibit calcium from entering the smooth muscles of blood vessels, resulting in relaxation and vasodilation. Diuretics promote the elimination of excess fluid and sodium from the body, reducing blood volume and thereby lowering blood pressure.
Antihypertensive agents are typically prescribed based on the individual patient's condition and specific needs. They can be used alone or in combination to achieve optimal blood pressure control. It is important to note that antihypertensive agents should be taken regularly as prescribed by a healthcare professional and may require periodic monitoring to ensure their effectiveness and manage any potential side effects.
In summary, antihypertensive agents play a vital role in the management of hypertension by targeting various mechanisms involved in blood pressure regulation. These medications offer significant benefits in reducing the risk of cardiovascular complications associated with high blood pressure.
Triamterene API manufacturers & distributors
Compare qualified Triamterene API suppliers worldwide. We currently have 2 companies offering Triamterene API, with manufacturing taking place in 2 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Ipca Labs. | Producer | India | Unknown | CEP, CoA, FDA, GMP, USDMF | 69 products |
| Moehs | Producer | Spain | Spain | CEP, CoA, EDMF/ASMF, GMP, JDMF, USDMF | 50 products |
When sending a request, specify which Triamterene API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
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