Aceclofenac -  Pharmacodynamics, Pharmacokinetic, Uses, Doses, Adverse Effect, Precautions and Drug Interaction

Generic Name

 Aceclofenac

Summery

 Aceclofenac is a nonsteroidal anti-inflammatory drug (NSAID) analog of diclofenac. It is used for the relief of pain and inflammation in rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

It is reported to have a higher anti-inflammatory action or at least comparable effects than conventional NSAIDs in double-blind studies.

Aceclofenac potently inhibits the cyclo-oxygenase enzyme (COX) that is involved in the synthesis of prostaglandins, which are inflammatory mediators that cause pain, swelling, inflammation, and fever.

It was patented in 1983 and approved for medical use in 1992.

Structure

Molecular Weight

Molar mass: 354.1847 g/mol

Chemical formula

Formula: C16H13Cl2NO4

IUPAC Name 

[[[2-[(2,6-Dichlorophenyl)amino]phenyl]acetyl]oxy]acetic acid.

Pharmacology

Indication

Pain & Inflammation

Ankylosing Spondylitis (AS)

Osteoarthritis (OA)

Rheumatoid Arthritis

Pharmacodynamics

 Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade.

COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli.

Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs.

The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM.

Mechanism of Action

Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2).

Aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF).

It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils.

Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects.

Absorption

Aceclofenac is rapidly and completely absorbed from the gastrointestinal tract and circulates mainly as unchanged drug following oral administration.

Peak plasma concentrations are reached around 1.25 to 3 hours post-ingestion, and the drug penetrates into the synovial fluid where the concentration may reach up to 60% of that in the plasma. 

There is no accumulation in regular dosing, with similar maximum plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) after single and multiple doses

Volume of Distribution

 Approximately 25 L

Protein Binding

Highly protein-bound (>99%)

Metabolism

4'-hydroxyaceclofenac is the main metabolite detected in plasma however other minor metabolites include diclofenac, 5-hydroxyaceclofenac, 5-hydroxydiclofenac, and 4'-hydroxydiclofenac

Route of Elimination

Urine 70-80% as glucuronidated and hydroxylated forms of aceclofenac.

About 20% of the dose is excreted into feces

Half Life

Approximately 4 hours

Clearance

Approximately 5 L/h

Doses

 Body Weight – 2mg/kg every 12 hours.

Adult - 100mg Tablet to be taken twice after meal.

Adverse Effects

Gastro-intestinal disorders (dyspepsia, abdominal pain, nausea),

Skin rash,

Loss of Appetite,

Visual Disturbance,

Urticaria,

Symptoms of enuresis,

Headache,

Dizziness, and drowsiness 

Precautions 

Allergies – Avoid if you have a known allergy to Aceclofenac or other NASIDs.

Asthma – Aceclofenac is not recommended in asthma.

Bleeding – if you have any bleeding disorder, Aceclofenac is not recommended.

Pregnancy – not recommended to pregnant women.

Breast Feeding –not recommended for breast feeding women.

Cardiac Surgery –Not recommended after and before coronary artery bypass surgery.

Impaired Kidney Function – Not Recommended.

Impaired Liver Function – mild liver falure 100mg once daily, contraindicated in severe liver failure.

Drug Interaction

Abacavir - Decrease the excretion rate of Abacavir.

Abciximab - The risk or severity of bleeding and hemorrhage can be increased.

Acebutolol - Decrease the antihypertensive activities of Acebutolol.

Acemetacin - The risk or severity of adverse effects can be increased.

Acenocoumarol - The risk or severity of bleeding and hemorrhage can be increased.

Aceclofenac -  Pharmacodynamics, Pharmacokinetic, Uses, Doses, Adverse Effect, Precautions and Drug Interaction PDF Notes