PHARMACOKINETICS
SAFENAC-P is a fixed dose combination of Aceclofenac and Paracetamol. Aceclofenac belongs to a group of Non Steroidal Anti-inflammatory Drugs (NSAIDs) used to treat various painful inflammatory conditions. Aceclofenac has an outstanding anti-inflammatory profile mediated primarily through inhibition of cyclooxygenase (COX) activity and suppression of PGE2 synthesis. Paracetamol is a safe and effective analgesic-antipyretic agent with minimal effect on cardiovascular, respiratory and GI system. Paracetamol or acetaminophen is the deethylated active metabolite of phenacetin. Chemically, Paracetamol is N-acetyl-p-aminophenol.

Aceclofenac is well absorbed from gastrointestinal tract and peak plasma concentrations (Cmax) are reached 1-3 hours after an oral dose. The drug is more than 99% bound to plasma proteins and the volume of distribution (Vd) is approximately 25 liters. The presence of food reduced rate of absorption (increased tmax) but not the extent of absorption (Cmax or AUC). 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. Aceclofenac is metabolized mainly to 4’ hydroxyaceclofenac. The drug is eliminated primarily through renal excretion with 70-80% of administered dose found in urine as glucoronides and rest being excreted in faeces. The plasma elimination half-life of Aceclofenac is approximately 4 hours.

Paracetamol is rapidly and almost completely absorbed from gastrointestinal tract with peak plasma concentrations (Cmax) occurring about 10 to 60 minutes after oral administration. Plasma protein binding is negligible at usual therapeutic concentration but increases with increasing concentrations. Acetaminophen is relatively uniformly distributed throughout most body fluids. The plasma half-life (t1/2) 2-3 hours and the effect after oral dose lasts for 3-5 hours. Paracetamol is metabolized predominantly in liver and excreted in the urine mainly as glucuronide and sulfate conjugate. Less than 5% is excreted unchanged.

DESCRIPTION
Trypsin: is serine endopeptidase that catalyses the clevage of peptide bonds on the carboxyl side of either arginine or lysine. A wide range of therapeutic benefits of trypsin are fibrolytic activity, regulates cytokinase levels and scavenges free radicals. it enhances prolteolysis and thrombolysis to promote wound healing.
Bromelain: breaks peptide bonds inside protein molecules. It acts as an anti-coagulant and anti-fibronolytic agents , prolongs the adhesion of platelets to endothelial cells of blood vessel, prevents edema formation and reduces existing edema. supprt skin debriment of burns and removes cell debris by activating macrophage
Rutoside: is the rutinose glycoside form of quercetin whose absoprtion appears to occur mainly from colon following the removal of the carbohydrates moiety. It increases the strength of the walls of the blood capillaries and regulates the permeability so as to normalize pathogically increased vessel permeability. It is known to have beneficial effects on capillary disorders. It also has antioxidant activity, as well as anti-inflammatory , antihistaminic and antiviral properties

Benefits of the Combination
Based on the studies carried out, with the combination of enzymes against diclofenac in osteoarthiritic patients, iit was concluded that the above enzyme combination can be considered as an effective alternative to non-steroidal anti-inflammatory drugs such as diclofenac in the treatment of painful episode of knee osteoarthiritis
INDICATION: Pain and Inflammation
DOSAGE: Adult- 1-2 tablets BID/TID or as prescribed by a physician
PRECAUTIONS
Bromelain + Trypsin + Rutoside are contraindicated in hepatic and/or renal disorder patients, patients with bleeding disorders, menorrhagia, hematuria and hematemesis. Bromelain + Trypsin + Rutoside is contraindicated in patients with an allergy to cypress pollen, pineapple, papain, carrot, grass pollen and fennel. Bromelain + Trypsin + Rutoside may increase the risk of bleeding during and after surgery. Discontinue Bromelain + Trypsin + Rutoside use at least two weeks before surgery to avoid bleeding disorders

INDICATIONS:
ENZOBOND is indicated for relief from severe pain and inflammation in Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis, Low back pain, Dental pain, Gynaecological pain and painful & Inflammatory conditions of ear, nose & throat.
OTHER DRUG INTERACTIONS
Bromelain + Trypsin + Rutoside may interact with tetracycline group of drugs, amoxicillin, aspirin, NSAIDs, anticoagulants including clopidogrel.
OTHER INTERACTIONS
Bromelain + Trypsin + Rutoside may interact with zinc, potato, soybean, licorice, quassia, willow, red clover, celery, meadowsweet, fenugreek, arnica, alfalfa, asafoetida, chestnut, chamomile, clover, ginger, garlic and angelica.