Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antiinflammatory and antirheumatic products, non-steroids, oxicams ATC code: M 01 AC 05

Lornoxicam is a non steroidal anti-inflammatory drug with analgesic properties and belongs to the class of oxicams. Lornoxicam's mode of action is mainly related to the inhibition of the prostaglandin synthesis (inhibition of the cyclooxygenase enzyme), leading to desensitisation of peripheral nociceptors and consequently inhibition of inflammation. A central effect on nociception which seems to be independent of anti- inflammatory effects has also been suggested.

Lornoxicam has no effect on vital signs (e.g. body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry).

The analgesic properties of lornoxicam have been demonstrated successfully in several clinical trials during development of the drug.

Due to a local gastrointestinal irritation and a systemic ulcerogenic effect related to the inhibition of prostaglandin (PG)-synthesis, gastrointestinal sequela are common undisirable effects after treatment with lornoxicam as seen with other NSAIDs.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Lornoxicam is absorbed rapidly and almost completely from the gastrointestinal tract. Maximum plasma concentrations are achieved after approx. 1-2 hours. The absolute bioavailability of lornoxicam is 90-100%. No first-pass effect was observed. The mean elimination half-life is 3 to 4 hours.
Simultaneous intake of lornoxicam with meals reduced C max by approx. 30%. Tmax was increased from 1.5 to 2.3 hours. The absorption of lornoxicam (calculated on AUC) can be reduced up to 20%.
Distribution
Lornoxicam is found in the plasma in unchanged form and as its hydroxylated metabolite. The plasma protein binding of lornoxicam is 99% and not concentration dependent.
Biotransformation
Lornoxicam is extensively metabolised in the liver, primarily to the inactive 5–hydroxylornoxicam by hydroxylation. CYP2C9 is involved in this biotransformation of lornoxicam. Due to genetic polymorphism slow and extensive metabolisers exist for this enzyme, which could result in markedly increased plasma levels of lornoxicam in slow metabolisers. The hydroxylated metabolite exhibits no pharmacological activity. Lornoxicam is metabolized completely, and approximately 2/3 is eliminated via the liver and 1/3 via the kidneys as inactive substance.

When tested in animal models, lornoxicam did not induce liver enzymes. From clinical trial data there is no evidence of accumulation of lornoxicam after repeated administrations, when given according to recommended dosage. This finding was supported by drug monitoring data from 1 year studies.

Elimination
The mean elimination half-life of the parent compound is 3 to 4 hours. After oral administration about 50% is excreted in the faeces and 42% through the kidneys, mainly as 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam is about 9 hours after a parenteral single or twice daily dose.


In elderly patients above 65, the clearance is reduced with 30-40 %. Apart from this reduced clearance there is no significant change in the kinetic profile of lornoxicam in elderly patients.
There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic failure, except for accumulation in patients with chronic liver disease after 7 days of treatment with daily doses of 12 and 16 mg.