(S)-(+)-Ketoprofen

Absorption

After oral ingestion, the Dexketoprofen onset of action is within 30 minutes. The plasma half-life of Dexketoprofen is about 4-6 hours. The Cmax is about 30 minutes

Toxicity

Nausea and/or vomiting, stomach pain, diarrhea, digestive problems (dyspepsia) are the most common symptoms of toxicity. More toxicity symptoms include dizziness, sleepiness, disturbed sleep, nervousness, headache, palpitations, flushing, stomach problems, constipation, dry mouth, flatulence, skin rash, tiredness, pain, feeling feverish and shivering, and malaise.
Severe toxicity can lead to thrombocytopenia and anemia with bleeding episodes. Dexketoprofen is associated with a small increased risk of myocardial infarction .

Chemical properties

White Solid

The Uses of (S)-(+)-Ketoprofen

Anti-inflammatory; analgesic

The Uses of (S)-(+)-Ketoprofen

COX inhibitor

Indications

For short-term treatment of mild to moderate pain, including dysmenorrhoea, musculoskeletal pain and toothache .

Background

Dexketoprofen is a non-steroidal anti-inflammatory drug. It is available in the various countries in Europe, Asia and Latin America. It has analgesic, antipyretic and anti-inflammatory properties .

What are the applications of Application

(S)-(+)-Ketoprofen is a Cox inhibitor

What are the applications of Application

(S)-Ketoprofen is an inhibitor of TXB2 generation and of Cox

Definition

ChEBI: A monocarboxylic acid that is (S)-hydratropic acid substituted at position 3 on the phenyl ring by a benzoyl group. A cyclooxygenase inhibitor, it is used to relieve short-term pain, such as muscular pain, dental pain and dysmenorrhoea.

Biological Activity

(s)-ketoprofen, a dual cox1/2 inhibitor, can be used as a nonsteroidal anti-inflammatory drug to treat arthritis-related inflammatory pains. ketoprofen is photolabile and undergoes degradation when irradiated by sunlight to induce various skin diseases [1].

Pharmacokinetics

This drug is an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties .

in vitro

the combination of uvb irradiation with ketoprofen dose-dependently induced the cytotoxicity and suppressed dna synthesis in hacat cells. uvb-irradiated kp inhibited the cell growth and induced g2/m cell cycle arrest by regulating the levels of cdc2, cyclin b1, chk1, tyr15-phosphorylated cdc2 and p21. the dapi staining results has revealed that kp accentuated the apoptotic response to uvb radiation in hacat cells [1].

in vivo

in a placebo-controlled, double-blind study in the rhesus monkeys macaca mulatta with periodontal disease, administeration of kp at 1% level in suitable topical vehicles to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months effectively inhibited gcf-ltb4 and gcf-pge2 and positively altered alveolar bone activity [2]. ketoprofen at a dose of 3.63 mg/kg bwt (phenylbutazone equimolar dose) showed significant analgesic effects and reduced hoof pain and lameness to a greater extent [3]. treatment with ketoprofen (40 and 80 mg/kg diet) greatly reduced the incidence of transitional cell carcinoma of the urinary bladder by >70% from that seen in dietary mice [4].

Drug interactions

Potentially hazardous interactions with other drugs
ACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia
Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects);avoid with ketorolac (increased risk of side effects and haemorrhage).
Antibacterials: possibly increased risk of convulsions with quinolones
Anticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban
Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine.
Antidiabetic agents: effects of sulphonylureas enhanced.
Antiepileptics: possibly increased phenytoin concentration.
Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir.
Ciclosporin: may potentiate nephrotoxicity.
Cytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.
Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect, hyperkalaemia with potassium-sparing diuretics.
Lithium: excretion decreased.
Pentoxifylline: increased risk of bleeding
Probenecid: excretion reduced by probenecid.
Tacrolimus: increased risk of nephrotoxicity

Metabolism

Dexketoprofen is highly lipophilic, and is metabolized in the liver by glucuronidation . In one study, after oral administration of 25 mg of dexketoprofen to young healthy adults, Tmax was approximately 30 min for a Cmax of 3.7 ± 0.72 mg/l . Dexketoprofen trometamol is metabolized by the hepatic cytochrome P450 enzymes (CYP2C8 and CYP2C9) .
Dexketoprofen trometamol has a number of metabolites, with hydroxyl derivatives making up the greatest volume . In humans, hydroxylation plays a minor role.
Dexketoprofen is primarily conjugated to an acyl-glucuronide

Metabolism

Dexketoprofen is the S-enantiomer of ketoprofen.The main elimination route for dexketoprofen is glucuronide conjugation in the liver followed by renal excretion.

References

[1]. liu s, mizu h, yamauchi h. molecular response to phototoxic stress of uvb-irradiated ketoprofen through arresting cell cycle in g2/m phase and inducing apoptosis[j]. biochemical and biophysical research communications, 2007, 364(3): 650-655.
[2]. li k l, vogel r, jeffcoat m k, et al. the effect of ketoprofen creams on periodontal disease in rhesus monkeys[j]. journal of periodontal research, 1996, 31(8): 525-532.
[3]. owens j g, kamerling s g, stanton s r, et al. effects of ketoprofen and phenylbutazone on chronic hoof pain and lameness in the horse[j]. equine veterinary journal, 1995, 27(4): 296-300.
[4]. hawk e t, kelloff g j, mccormick d l. differential activity of aspirin, ketoprofen and sulindac as cancer chemopreventive agents in the mouse urinary bladder[j]. carcinogenesis, 1996, 17(5): 1435-1438.