Dexketoprofen

Dexketoprofen is an NSAID that represents the active (S)-enantiomer of the racemic drug ketoprofen. It belongs to the arylpropionic acid class of NSAIDs, which also includes drugs like ibuprofen and naproxen. Dexketoprofen exhibits analgesic, anti-inflammatory, and antipyretic properties, and it works by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the synthesis of prostaglandins, substances that promote inflammation, pain, and fever. Dexketoprofen was developed to provide a more potent and faster-acting option compared to racemic ketoprofen, as it uses only the active (S)-enantiomer, which is responsible for the majority of the drug's therapeutic effects. This results in a potentially faster onset of pain relief and a lower risk of gastrointestinal side effects, making it more tolerable for short-term use.

Approved in Europe in 1998, dexketoprofen is widely used in Europe, Latin America, and Asia, but has not been approved by the U.S. FDA or Health Canada. It remains a popular choice for acute pain relief, particularly when fast action is needed.

BRAND NAMES

Enantyum: Enantyum is primarily used for managing acute pain, such as musculoskeletal pain, dental pain, and dysmenorrhea (painful menstruation). 25 mg tablets for oral use and 25 mg/2 mL injectable solution for parenteral administration.

Deksalgin: Deksalgin is used for the treatment of acute pain, such as that caused by dysmenorrhea, arthritis, and postoperative conditions. 25 mg tablets for oral use and 25 mg/2 mL injectable solution.

MECHANISM OF ACTION

Dexketoprofen is a non-steroidal anti-inflammatory drug (NSAID) that works by inhibiting both COX-1 and COX-2 enzymes. These enzymes are responsible for the production of prostaglandins, which mediate pain, inflammation, and fever. By reducing prostaglandin synthesis, dexketoprofen effectively alleviates pain and inflammation.

PHARMACOKINETICS

Absorption:

Dexketoprofen is rapidly absorbed after oral administration. Peak plasma concentrations are typically reached within 30 to 60 minutes. Its bioavailability is around 80% when taken orally.

Distribution:

The drug is widely distributed throughout the body, with high plasma protein binding (99%) to albumin. It has a volume of distribution (Vd) of approximately 0.1 L/kg.

Metabolism:

Dexketoprofen is extensively metabolized in the liver by cytochrome P450 enzymes, particularly CYP2C9. The drug is converted into inactive metabolites that are then excreted in the urine.

Elimination:

The elimination half-life of dexketoprofen is around 1.5 to 2 hours, meaning it is cleared relatively quickly from the body. The drug is primarily excreted in the urine as metabolites (over 90%), with a small fraction excreted in feces.

DOSAGE AND ADMINISTRATION

Dexketoprofen is typically dosed at 25 mg every 8 hours for adults, with a maximum of 75 mg per day, and should be taken with food to minimize gastrointestinal irritation. For injectable forms, the dose is also 25 mg every 8 hours, with the same maximum daily dose. In elderly patients or those with renal or hepatic impairments, dosage adjustments may be necessary, and careful monitoring is advised. The drug is generally intended for short-term use due to potential side effects, such as gastrointestinal and renal complications, with regular monitoring recommended for patients on prolonged therapy.

CONTRAINDICATIONS

Hypersensitivity to dexketoprofen, ketoprofen, or other NSAIDs.
History of asthma, bronchospasm, rhinitis, or urticaria after taking NSAIDs or aspirin.
Active peptic ulcer, gastrointestinal bleeding, or a history of recurrent ulceration or bleeding.
Severe heart failure, hepatic failure, or renal failure.
Bleeding disorders or ongoing anticoagulant therapy.
Pregnancy (especially third trimester) and lactation.
Children and adolescents (not recommended due to lack of safety data).
Cerebrovascular or other active bleeding conditions.
Dehydration due to vomiting, diarrhea, or inadequate fluid intake, increasing the risk of renal toxicity.

DRUG INTERACTIONS

Anticoagulants (e.g., warfarin, heparin) and antiplatelet agents (e.g., aspirin, clopidogrel): Higher risk of bleeding due to additive anticoagulant effects.
Diuretics (e.g., furosemide, thiazides): Reduced diuretic efficacy and increased risk of nephrotoxicity, especially in dehydrated patients.
ACE Inhibitors and ARBs (e.g., enalapril, losartan): May reduce antihypertensive effects and increase risk of renal dysfunction.
Lithium: Increased serum lithium levels and potential lithium toxicity.
Methotrexate: Increased risk of methotrexate toxicity, especially at high doses.
Selective Serotonin Reuptake Inhibitors (SSRIs): Additive risk of gastrointestinal bleeding.
Digoxin: Possible increase in digoxin plasma concentrations.
Cyclosporine and Tacrolimus: Increased risk of nephrotoxicity.
Alcohol: Enhanced gastrointestinal irritation and risk of bleeding.

SIDE EFFECTS