Sulfinpyrazone is a uricosuric drug primarily used to prevent gout by promoting the renal excretion of uric acid, thereby reducing serum urate levels and the risk of urate crystal deposition in joints and tissues. It acts by inhibiting urate reabsorption in the proximal renal tubules. First developed in the 1950s, sulfinpyrazone was introduced as an alternative to existing gout therapies such as colchicine and allopurinol, particularly for patients who required uric acid-lowering treatment but could not tolerate other medications. Over time, it has also been recognized for its mild antiplatelet effects, which can contribute to the prevention of thromboembolic events, expanding its clinical utility beyond gout management.
BRAND NAMES
Some common brand names for sulfinpyrazone include:
Anturane – the most widely recognized brand
ESPUTAN – less common, used in some regions
Brand availability can vary by country, and generic versions are often labeled simply as sulfinpyrazone.
MECHANISM OF ACTION
Sulfinpyrazone exerts its effects through two primary mechanisms. First, it lowers serum uric acid levels and helps prevent gout attacks by promoting uric acid excretion via inhibition of its reabsorption in the renal tubules. Second, it has an antithrombotic effect by inhibiting platelet aggregation, achieved through the suppression of thromboxane A2 synthesis, which reduces the risk of blood clot formation.
PHARMACOKINETICS
Absorption
Sulfinpyrazone is well absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are typically reached within 2–4 hours. Food may slightly delay the rate of absorption but does not significantly affect the overall extent of absorption or its clinical effectiveness. The drug is highly bound to plasma proteins, which can influence its distribution in the body.
Distribution
The volume of distribution of sulfinpyrazone is relatively low, reflecting its high plasma protein binding (approximately 98–99%). Reported values are around 0.2–0.3 L/kg, indicating that the drug largely remains within the vascular compartment rather than distributing extensively into tissues.
Metabolism
Sulfinpyrazone is extensively metabolized in the liver, primarily via oxidation and conjugation reactions. Its metabolism produces several inactive metabolites that are then excreted in the urine and feces. Hepatic metabolism plays a significant role in determining the drug’s plasma levels and duration of action, and any liver impairment can alter its pharmacokinetics, potentially increasing the risk of adverse effects.
Excretion
Sulfinpyrazone is rapidly and completely excreted, with over 95% recovered within four days, primarily in the urine (85%) and partly in the feces (10%).
PHARMACODYNAMICS
Sulfinpyrazone’s pharmacodynamic profile is characterized by a potent uricosuric action that lowers serum uric acid levels through inhibition of its renal tubular reabsorption. Additionally, it exhibits an antithrombotic effect by preventing platelet aggregation via suppression of thromboxane A₂ synthesis. Although it lacks significant anti-inflammatory and analgesic activity, sulfinpyrazone can also inhibit various transport proteins, including hURAT1, hOAT4, and multiple drug resistance proteins (MRPs).
DOSAGE AND ADMINISTRATION
Sulfinpyrazone is administered orally, usually in divided doses with food or milk to minimize gastrointestinal irritation.
For gout (chronic management):
The usual adult dosage is 200–400 mg per day, given in two divided doses. Depending on response and tolerance, the dose may be increased up to 800 mg daily in divided doses.
Therapy should be initiated after an acute gout attack has subsided, as starting treatment during an attack may exacerbate symptoms.
For antiplatelet therapy (off-label use):
Doses of 200 mg twice daily have been used to inhibit platelet aggregation and reduce thromboembolic risk, though this indication is less common today.
DRUG INTERACTIONS
Sulfinpyrazone interacts with several drugs by affecting hepatic metabolism, protein binding, and renal excretion. It can enhance the effects of warfarin and hypoglycemic agents, while salicylates and diuretics may reduce its uricosuric action. It may also increase plasma levels of theophylline and phenytoin. Careful monitoring is advised when used with these medications.
FOOD INTERACTIONS
Food has minimal effect on the absorption or overall effectiveness of sulfinpyrazone. However, taking the drug with food or milk is recommended to help reduce gastrointestinal irritation. Maintaining adequate fluid intake during therapy is also important to prevent uric acid stone formation.
CONTRAINDICATIONS
Sulfinpyrazone is contraindicated in patients with conditions that may be worsened by its pharmacologic effects. It should not be used in individuals with a history of hypersensitivity to sulfinpyrazone or other pyrazolone derivatives. It is also contraindicated in patients with active peptic ulcer disease, blood dyscrasias, or significant hepatic or renal impairment, as these conditions increase the risk of toxicity. Additionally, it should be avoided during acute gout attacks, since uricosuric therapy can exacerbate symptoms. Caution is advised in patients with a history of uric acid kidney stones due to the risk of stone formation.
SIDE EFFECTS
Gastrointestinal issues.
Initial gout flares.
Drowsiness.
Kidney problems.
Blood disorders.
Severe allergic reactions.
Gastrointestinal bleeding.
Swollen or painful glands.
Increased blood pressure.
Dizziness or unsteadiness.
Weight gain.
OVERDOSE
Severe or persistent nausea, vomiting, or diarrhea.
Severe or persistent stomach pain, especially epigastric (upper abdomen) pain.
Clumsiness or unsteadiness (ataxia).
Labored or difficult breathing.
Convulsions (seizures), which may be followed by coma.
TOXICITY
Sulfinpyrazone toxicity primarily involves adverse effects on the gastrointestinal, hematologic, hepatic, and renal systems. Common signs of toxicity include nausea, vomiting, abdominal pain, and gastrointestinal bleeding due to mucosal irritation. Hepatotoxicity and bone marrow suppression (such as agranulocytosis or aplastic anemia) are rare but potentially serious complications. Overdose may lead to central nervous system symptoms like dizziness, confusion, or seizures. Because the drug is extensively metabolized in the liver, toxicity risk increases in patients with hepatic impairment. Management is mainly supportive and symptomatic, with attention to maintaining adequate hydration, correcting electrolyte imbalances, and monitoring renal and hepatic function. Discontinuation of the drug is essential if severe adverse reactions occur.
