Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1. Pharmacodynamic properties
Anti-inflammatory and antirheumatic products, non-steroids, ATC code: M01AE03 (M: musculo-skeletal system)

Ketoprofen is a non-steroidal anti-inflammatory drug derived from aryl carboxylic acid, and belongs to the propionic group. It has the following properties:
• peripheral and central analgesic properties,
• antipyretic properties,
• anti-inflammatory properties,
• short-term inhibition of platelet function.
All of these properties are related to prostaglandin synthesis inhibition.

In several experimental models, a central analgesic effect was observed for ketoprofen, as with other NSAIDs.

Pharmacokinetic Properties

5.2. Pharmacokinetic properties
Absorption
Successive serum level determinations after administration of a therapeutic dose show that ketoprofen is very rapidly absorbed. Peak serum concentrations were reached 60 to 90 minutes after oral administration.
After rectal administration, the time to peak serum concentration is 45 to 60 minutes.
When ketoprofen is administered with food, the absorption rate is slower, causing delayed and reduced peak plasma concentrations (Cmax). However, total bioavailability remains unchanged.


Distribution
Following oral administration, the mean plasma elimination half-life is approximately 1.5 to 2 hours.
Following rectal administration, the mean plasma elimination half-life is 2.2 hours.
Ketoprofen is 99% plasma protein bound.

Ketoprofen is distributed into and remains in synovial fluid at concentrations higher than serum th concentrations after the 4 hour following oral administration.

It crosses the placental and blood-brain barriers.

The volume of distribution is approximately 7 l.
Metabolism

Biotransformation of ketoprofen is characterized by two processes: a very minor process (hydroxylation) and a largely predominant process (glucuronide conjugation).

Less than 1% of the administered ketoprofen dose is recovered unchanged in the urine, while the glucuronide metabolite accounts for approximately 65 to 75%.

Excretion

Profenid® 50 mg hard capsules
Within 5 days of oral administration, 75 to 90% of the dose is excreted by the renal route and 1 to 8% in the feces.

Ketoprofen excretion, mainly in the urine, is rapid since 50% of the administered dose is eliminated within 6 hours, irrespective of the route of administration.

Pathophysiological changes
• Elderly subjects: the absorption of ketoprofen does not change, but the elimination half-life is longer (3 hours).
• Patients with renal insufficiency: total clearance is prolonged in proportion to the extent of renal insufficiency.

Profenid® 100 mg suppositories

Ketoprofen excretion, mainly in the urine, is rapid since 50% of the administered dose is eliminated within 6 hours, irrespective of the route of administration.
Pathophysiological changes
• Elderly subjects: the elimination half-life is longer.
• Patients with renal insufficiency: total clearance is prolonged in proportion to the extent of renal insufficiency.