Actions of Mahanac in details
Pharmacology: Mahanac is a nonsteroidal agent with marked anti-inflammatory and analgesic properties. It has higher anti-inflammatory action than conventional NSAIDs and is a cytokine inhibitor. The mode of action of Mahanac is largely based on the inhibition of prostaglandin synthesis. Mahanac is a potent inhibitor of the enzyme cyclooxygenase, inflammatory cytokines interleukin IL1, tumor necrosis factor and prostaglandins E2. Cyclooxygenase is involved in the production of prostaglandins (chemicals in the body) which cause pain, swelling and inflammation.
Pharmacokinetics: After oral administration, Mahanac is rapidly and completely absorbed as unchanged drug. Peak plasma concentrations are reached approximately 1-3 hrs following ingestion. Mahanac is highly protein bound (>99%). Mahanac penetrates into the synovial fluid, where the concentrations reach approximately 57% of those in plasma. The volume of distribution is approximately 25 L. The mean plasma elimination t½ is around 4 hrs. Mahanac is metabolized to a major metabolite 4'-hydroxyaceclofenac and other metabolites 5 hydroxyaceclofenac, 4'-hydroxydiclofenac, diclofenac and 5 hydroxydiclofenac.
Approximately 2/3 of the administered dose is excreted via the urine, mainly as hydroxymetabolites. No changes in the pharmacokinetics of Mahanac have been detected in the elderly.
Mahanac administration
Should be taken with food. Take w/ or immediately after meals.
Mahanac pharmacology
After intake is absorbed from the gastrointestinal tract. Eating slows down the rate of absorption, extent of absorption is not changed. About 50% of the active substance is metabolized in the "first passage" through the liver. When used rectally absorption is slower. Time to reach Cmax in plasma after oral administration is 2-4 hours depending on the used dosage form, after rectal - 1 h, I.M. administration - 20 min. The concentration of active substance in plasma is a linear function of the applied dose.
Not cumulative. Plasma protein binding is 99.7% (predominantly albumin). Penetrates into synovial fluid, Cmax is achieved in 2-4 hours later than in plasma.
To a large extent metabolized to form several metabolites, among which two pharmacologically active, but to a lesser extent than diclofenac.
Systemic clearance of the active substance is about 263 ml / min. T1/2 from plasma is 1-2 h, from synovial fluid - 3-6 h. Approximately 60% of the dose was excreted as metabolites by the kidneys, less than 1% excreted in the urine as unchanged, while the rest is displayed in the form of metabolites with bile.
References
- EPA DSStox. "Aceclofenac: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
