Pharmacodynamics
Phenylbutazone is a synthetic pyrazolone derivative. The analgesic effect results from inhibition of the production of prostaglandin H and prostacyclin zu. Prostaglandins act on a variety of cells, such as vascular smooth muscle cells, platelets, and nerve cells in the spinal cord that cause pain sensation. Prostacyclin causes vasoconstriction and inhibits platelet aggregation. Phenylbutazone acts by binding and inhibiting prostaglandin H synthase and prostacyclin synthase. The decreased production of prostaglandin then results in less inflammation of surrounding tissues.
Pharmacokinetics
Phenylbutazone is almost completely absorbed in the small intestine and maximum plasma levels are reached after approximately 2 hours. The substance is present more than 95% bound to plasma proteins. The substance is metabolized in the liver and 70% is excreted by the kidney and about 30% by the biliary tract.
Interactions
Phenylbutazone is a CYP3A4 inducer and therefore may interact with a large number of drugs that are metabolized via CYP3A4. Phenylbutazone may therefore affect the blood levels and duration of action of the following drugs:
- Phenytoin
- Valproic acid
- Sulfonamides
- Sulfonylurea antidiabetics
- Barbiturates
- Promethazine
- Rifampicin
- Chlorpheniramine
- Diphenhydramine
- penicillin G
In addition, concomitant use with other anti-inflammatory drugs, such as corticosteroids and other NSAIDs, may promote increased formation of gastric ulcers and increase the risk of bleeding. Combination with anticoagulant drugs, especially coumarin derivatives, also increases the risk of bleeding.