Votan SR Mechanism of Action

Pharmacology: Pharmacodynamics: Votan SR F.C. Tablets 100 mg "S.T" contains a non-steroidal compound with pronounced antirheumatic, anti-inflammatory, analgesic, and antipyretic properties. Inhibition of prostaglandin biosynthesis, which has been demonstrated experimentally, is regarded as having an important bearing on its mechanism of action.
Pharmacokinetics: Diclofenac is completely absorbed from the sustained-release tablets. As a result of delayed release of the active substance, the peak plasma concentrations attained are lower than those achieved following the administration of conventional dosage forms. On the other hand, concentrations remain measurable for some hours after attaining their peak. Absorption sets in later following ingestion of a sustained-release tablet either with or after a meal than it does following administration on an empty stomach.
Since about half the active substance 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 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, concentrations of the 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 glucuronidation of the intact molecule but mainly single and multiple hydroxylation followed by glucuronidation. About 60% of the administered dose is excreted in the urine in the form of one of these two processes; less than 1% excreted as unchanged substance. The remainder of the dose is eliminated as metabolites through the bile in the feces.
No relevant age-dependent differences in the drug's absorption, metabolism, or excretion have been observed.
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 steady-state 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.