Dicloran Injection Mechanism of Action

Pharmacology: Pharmacodynamics: Dicloran contains a non steroidal compound with pronounced anti-inflammatory and analgesic properties. Inhibition of prostaglandin biosynthesis, which has demonstrated experimentally is regarded as having an important bearing on its mechanism of action. Prostaglandin plays an important role in the causation of inflammation, pain and fever.
In rheumatic diseases, the anti-inflammatory and analgesic properties of Dicloran elicit a clinical response characterized by marked relief from signs and symptoms such as pain at rest, pain on movement, morning stiffness, post traumatic inflammatory conditions.
Dicloran rapidly relieves both spontaneous pain and pain on movement and diminishes inflammatory swelling and wound oedema.
Pharmacokinetics: Approximately 20 minutes after intramuscular injection of 75 mg diclofenac, a mean peak plasma concentration of 2.5μg/ml (8μmol/litre) is attained.
The plasma concentration is in linear reaction to the dose. The area under the concentration curve (AUC) is about twice as large as it is following oral dose of equal size, because about half the active substance is metabolized during its first passage through the liver (first pass effect) when administered via the oral route.
Diclofenac becomes bound to serum proteins are at a rate of 99.7% chiefly to albumin (99.4%). The total systemic clearance of diclofenac in plasma is 263±56 ml/min (mean value ±SD). The terminal half life in plasma is 1-2 hours. Pharmacokinetic behavior remains unchanged following repeated administration. No accumulation occurs provided the recommended dosage intervals are observed. Diclofenac enters the synovial fluid where maximum concentrations are measured 2-4 hours after the peak plasma values have been attained.
The apparent half life for elimination from the synovial fluid is 3-6 hours. Only 4-6 hours after administration, therefore, concentration of active substance are already higher in the synovial fluid than they are in the plasma and remain higher for up to 12 hours.
The biotransformation of diclofenac involves partly glucordination of the intact molecule but mainly single and multiple hydroxylation followed by glucordination. About 60% of the administered dose is excreted in the urine in the form of metabolites from one of the two processes: less than 1% is excreted as unchanged substance in the faeces.
The age of the patient has no influence on the absorption, metabolism or excretion of diclofenac. 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 10 ml/min, the theoretical steadystate plasma levels of metabolites are about 4 times higher than in normal subjects. However the metabolites are ultimately cleared through the bile.
In the presence of impaired hepatic function (chronic hepatitis, non decompensated cirrhosis), the kinetics and metabolism of diclofenac are the same as in patients without liver disease.