Cataflam Mechanism of Action

Anti-inflammatory and anti-rheumatic product, non-steroid, acetic acid derivative.
Pharmacology: Mechanism of Action: Diclofenac, the active substance of Cataflam, is a non-steroidal compound with pronounced antirheumatic, anti-inflammatory, analgesic and antipyretic properties. Inhibition of prostaglandin biosynthesis, which has been demonstrated in experiments, is considered fundamental to its mechanism of action. Prostaglandins play a major role in causing inflammation, pain and fever.
Diclofenac in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached in humans.
Sugar-coated tablets: Cataflam tablets have a rapid onset of action which makes them particularly suitable for the treatment of acute painful and inflammatory conditions.
Pharmacodynamics: Cataflam has been found to exert a pronounced analgesic effect in moderate and severe pain. In the presence of inflammation, e.g., due to trauma or following surgical interventions, it rapidly relieves both spontaneous pain and pain on movement and diminishes inflammatory swelling and wound edema.
Sugar-coated tablets: Clinical studies have also revealed that in primary dysmenorrhea the active substance is capable of relieving the pain and reducing the extent of bleeding.
In migraine attacks Cataflam has been shown to be effective in relieving the headache and in improving the accompanying symptoms nausea and vomiting.
Clinical Studies: Cataflam is a well-established product.
Pharmacokinetics: Absorption: Diclofenac is rapidly and completely absorbed from diclofenac potassium tablets or the resinate suspension. The absorption sets in immediately after administration.
Since about half of diclofenac is metabolized during its first passage through the liver ("first pass" effect), the area under the concentration curve (AUC) is about half as large following oral or rectal administration as it is following a parenteral dose of equal size.
Pharmacokinetic behaviour does not change after repeated administration. No accumulation occurs provided the recommended dosage intervals are observed.
Sugar-coated tablets: The same amount is absorbed as from an equivalent dose of diclofenac sodium gastro-resistant tablets.
Mean peak plasma concentrations of 3.8 micromol/L are attained after 20 to 60 minutes after ingestion of one tablet of 50 mg.
Ingestion together with food has no influence on the amount of diclofenac absorbed although onset and rate of absorption may be slightly delayed.
Oral drops: After single administration of drops corresponding to 50 mg diclofenac sodium, peak plasma concentrations of about 0.5 micrograms/mL (1.63 micromol/L) are attained within 2 hours.
The plasma concentrations attained in children given equivalent doses (mg/kg body weight) are similar to those obtained in adults.
Distribution: 99.7% of diclofenac binds to serum proteins, mainly to albumin (99.4%). The apparent volume of distribution calculated is 0.12 to 0.17 L/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2 to 4 hours after peak plasma values have been reached. The apparent half-life for elimination from the synovial fluid is 3 to 6 hours. Two hours after reaching peak plasma levels, concentrations of the active substance are already higher in the synovial fluid than in the plasma, and they remain higher for up to 12 hours.
Biotransformation/metabolism: Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, resulting in several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-, 4',5-dihydroxy-, and 3'-hydroxy-4'-methoxy-diclofenac), most of which are converted to glucuronide conjugates.
Two of these phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
Oral drops: Biotransformation of diclofenac is quick and almost complete. The metabolites are known.
Elimination: Total systemic clearance of diclofenac from plasma is 263±56 mL/min (mean value±SD).
The terminal half-life in plasma is 1 to 2 hours. Four of the metabolites, including the two active ones, also have short plasma half-lives of 1 to 3 hours. One metabolite, 3'-hydroxy-4'-methoxydiclofenac, has a much longer plasma half-life. However, this metabolite is virtually inactive.
About 60% of the administered dose is excreted in the urine as the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates.
Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated as metabolites through the bile in the faeces.
Linearity/non-linearity: The amount absorbed is in linear proportion to the size of the dose.
Special populations: Geriatric patients: No relevant age-dependent differences in the drug's absorption, metabolism, or excretion have been observed.
Renal impairment: In patients suffering from renal impairment, no accumulation of the unchanged active substance can be inferred from the single-dose kinetics when applying the usual dosage schedule. At a creatinine clearance of less than 10 mL/min, the calculated steady-state plasma levels of the hydroxy metabolites are about 4 times higher than in normal subjects. However, the metabolites are ultimately cleared through the bile.
Hepatic impairment: In patients with chronic hepatitis or non-decompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Toxicology: Non-Clinical Safety Data: Preclinical data from acute and repeated dose toxicity studies, as well as from genotoxicity, mutagenicity, and carcinogenicity studies with diclofenac revealed no specific hazard for humans at the intended therapeutic doses.
For more information, see Use in Pregnancy & Lactation.