Chemical formula: C₁₃H₁₁N₃O₄S₂ Molecular mass: 337.37 g/mol PubChem compound: 54677971
Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) which has anti-inflammatory, analgesic, antipyretic properties and it also inhibits platelet aggregation. Tenoxicam reduces prostaglandin biosynthesis by inhibition of cyclooxygenase 1 (COX1) and 2 (COX2), both in vitro (sheep seminal vesicles) and in vivo (protection of arachidonic acid-induced toxicity in mice).
In-vitro investigation on cyclo-oxygenase isoenzymes prepared from human COS-7 cells have shown that tenoxicam inhibits COX-1 and COX-2 isoenzymes approximately to the same extent, i.e. COX-2/COX-1 ratio equals to 1.34.
In-vitro tests of leukocyte peroxidase suggest that tenoxicam may act as a scavenger for active oxygen at the site of inflammation.
Tenoxicam is a potent in-vitro inhibitor of human metalloproteinases (stromelysin and collagenase) which induce cartilage breakdown.
A further possible mechanism of action is the reduction of nitrite levels indicating an alteration of NO pathways.
These pharmacological effects explain, at least in part, the therapeutic benefit of tenoxicam in the treatment of painful inflammatory and degenerative disorders of the musculoskeletal system.
Tenoxicam is long-acting; a single daily dose is effective.
After oral administration, tenoxicam is rapidly and completely absorbed as unchanged drug. Concomitant food reduces the rate, but not the extent, of absorption of tenoxicam. Tenoxicam penetrates well into synovial fluid to give concentrations approximately half those in plasma. The mean plasma elimination half-life is approximately 72 hours.
With the recommended dosage regimen of 20mg once daily, steady-state plasma concentrations are reached within 10-15 days, with no unexpected accumulation. The average concentration at steady state is 11 mg/L when tenoxicam is given at oral doses of 20 mg once daily and this does not change even on treatment for up to four years.
Tenoxicam is strongly bound to plasma proteins. As predictable from single dose kinetic, plasma concentrations at steady state are 6-fold higher than those reached after a single dose.
The pharmacokinetics of tenoxicam are linear in the investigated dose range of 10 to 100 mg
No age-specific changes in the pharmacokinetics of tenoxicam have been found although inter-individual variation tends to be higher in elderly persons.
During the first two hours following intravenous administration of tenoxicam, plasma levels of the drug decline rapidly.
After this short period, no differences in plasma concentrations between intravenous and oral dosing are seen. The mean volume of distribution at steady state is 10 to 12 L.
In the blood over 99% of the drug is bound to albumin. Tenoxicam penetrates well into the synovial fluid. Peak concentrations are reached later than in plasma.
Tenoxicam is cleared from the body almost exclusively by metabolism. Approximately two-thirds of the administered dose is excreted in the urine, mainly as the pharmacologically inactive 5-hydroxypyridyl metabolite, and the remainder in the bile, much of it as glucuronide conjugates of hydroxy-metabolites. Less than 1% of the administered dose is recovered in the urine in form of the parent drug. The mean elimination half-life of tenoxicam is 72 hours (range 59 to 74 hours). The total plasma clearance is 2 mL/min.
Studies in the elderly and in patients with renal insufficiency or liver cirrhosis suggest that no dose adjustment is necessary to achieve plasma concentrations similar to those seen in healthy subjects.
Patients with rheumatic diseases and the elderly show the same kinetics profile as healthy volunteers.
Because of the high plasma protein binding of tenoxicam, caution is required when plasma albumin levels are markedly reduced.
Tenoxicam showed no carcinogenic effects in animals.
Tenoxicam showed no mutagenic effects in animals.
Tenoxicam showed no teratogenic effects in rats.
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