PHARMACOKINETICS OF ACHNIL INJECTION
ABSORPTION
The plasma peak concentration of controlled release injection of Aceclofenac is reached at 1 hr following injection.
DISTRIBUTION
The peak plasma concentration is reached in 1hr. More than 99% of Aceclofenac release injection is bound to plasma protein. As with other NSAIDs, Aceclofenac release injection diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverse and synovial fluid levels are higher than plasma level. In patients with knee pain and synovial fluid effusion, the plasma concentration of Aceclofenac was twice that in synovial fluid after multiple doses of the drug. The volume of distribution (Vd) is approximately 25 liters.
Aceclofenac Controlled Release profile:
In-vivo release of Aceclofenac: Controlled Release Injection is maintained within therapeutic window for 24 hours and there is burst release initially to control acute pain
Percentage cumulative in-vitro release of Aceclofenac injection: Controlled release is maintained till 24 hours after single injection and 50% of the drug is released in first 12 hours, indicating OD dose.
In vivo release of ACHNIL (Aceclofenac controlled release injection) is maintained within the therapeutic window for 24hours and there is burst release initially to control acute pain. Percentage cumulative in vitro release of Aceclofenac controlled release injection is maintained till 24hrs after single injection and 50% of the drug is released in first 12 hours, indicating OD.
METABOLISM
Aceclofenac is metabolized in human hepatocytes and human microsomes to form 4-hydroxy-Aceclofenac as the major metabolite, which is then further conjugated. Minor metabolites were 5-hydroxy-Aceclofenac and Diclofenac, 4-hydroxy-Diclofenac [11]. The other metabolites of Aceclofenac, namely Diclofenac and 4-hydroxy-Diclofenac, account for only 5% of the administered dose. Aceclofenac acts as a functional inhibitor of PGE2 production, either by acting directly on the production of cytokines that induce COX in the inflamed tissues or by its preferential intracellular conversion to COX-2 active metabolites, or most likely by both processes at the same time [4].
EXCRETION
About 65% of the administered dose is removed in the urine as hydroxy metabolites, and approximately 35% in the bile. The plasma elimination half life of Aceclofenac is approximately 4 hours.
