51146-56-6

Dexibuprofen, the S-(+)-isomer of the widely used NSAID agent ibuprofen, was launched in Austria for the treatment of rheumatoid arthritis. While the racemic compound is commonly used clinically, the antiinflammatory activity is mediated via the S-isomer by inhibition of prostaglandin synthesis. It has also been demonstrated that the R-isomer is converted to the Santipode in vivo via a CoA thioester intermediate. Since CoA plays a pivotal role in intermediary metabolism and maintenance of the [acyl-CoA], generation of R-ibuprofen-CoA competitively inhibits many CoA-dependent reactions, which consequently produces perturbations of hepatocyte Intermediary metabolism and mitocondrial function. Pure S-ibuprofen usage, therefore, is preferred allowing a reduction in dosage level and an improved side effect profile.

Ibuprofen is a non-steroidal anti-inflammatory drug with diverse biochemical actions, most notably inhibiting COX-1 and COX-2 (IC₅₀s = 2.6 and 1.53, μM, respectively). It is commonly synthesized as a racemic mixture of (S)- and (R)-isomers. (S)-Ibuprofen is an enantiomer that more potently inhibits COX activity, thromboxane formation, and platelet aggregation than the (R)-form. (S)-Ibuprofen also inhibits activation of NF-κB more effectively than (R)-ibuprofen (IC₅₀s = 62 and 122 μM, respectively). However, the enantiomers are equipotent in blocking superoxide formation, β-glucuronidase release, and LTB₄ generation by stimulated neutrophils (IC₅₀ values range from 0.14 to 0.58 μM). A majority of (R)-ibuprofen can be inverted to (S)-ibuprofen in humans after oral administration.

Colourless, Crystalline Solid

Gebro Broschek (Austria)

A nonsteroidal anti-inflammatory drug (NSAID); activity resides primarily in the (S)-isomer

Ibuprofen is a non-steroidal anti-inflammatory drug with diverse biochemical actions, most notably inhibiting COX-1 and COX-2 (IC50s = 2.6 and 1.53, μM, respectively). It is commonly synthesized as a racemic mixture of (S)- and (R)-isomers. (S)-Ibuprofen is an enantiomer that more potently inhibits COX activity, thromboxane formation, and platelet aggregation than the (R)-form. (S)-Ibuprofen also inhibits activation of NF-κB more effectively than (R)-ibuprofen (IC50s = 62 and 122 μM, respectively). However, the enantiomers are equipotent in blocking superoxide formation, β-glucuronidase release, and LTB4 generation by stimulated neutrophils (IC50 values range from 0.14 to 0.58 μM). A majority of (R)-ibuprofen can be inverted to (S)-ibuprofen in humans after oral administration.

sedative

ChEBI: Dexibuprofen is an ibuprofen. It has a role as a non-narcotic analgesic and a non-steroidal anti-inflammatory drug. It is an enantiomer of a levibuprofen.

Seractil

Non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase 1 and cyclooxygenase 2 (IC 50 values are 12 and 80 μ M respectively). Active isomer of ibuprofen.

NSAID and analgesic

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.
Tacrolimus: increased risk of nephrotoxicity

Dexibuprofen is the S(+)-enantiomer of ibuprofen. After metabolic transformation in the liver (hydroxylation and carboxylation), the pharmacologically inactive metabolites are completely excreted, mainly by the kidneys (90%), but also in the bile.

Store at -20°C

Crystallise the (+) and (-) acids from EtOH or aqueous EtOH. The racemate which crystallises from pet ether with m 75-77o is sparingly soluble in H2O and has IR (film) 1705 (C=O), 2300—3700 (OH broad)cm-1. It is used as a non-steroidal anti-inflammatory. [Shiori et al. J Org Chem 43 2936 1978, Kaiser et al. J Pharm Sci 65 269 1976, J Pharm Sci 81 221 1992, Freer Acta Cryst (C) 49 1378 1993 for the (S+)-enantiomer.]

[1] JIM BARNETT . Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system[J]. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1994, 1209 1: Pages 130-139. DOI: 10.1016/0167-4838(94)90148-1
[2] NICOLE SCHEUREN. Modulation of transcription factor NF-κB by enantiomers of the nonsteroidal drug ibuprofen[J]. British Journal of Pharmacology, 2009, 123 4: 645-652. DOI: 10.1038/sj.bjp.0701652
[3] M. VILLANUEVA. Equipotent inhibition by R(?)?, S(+)- and racemic ibuprofen of human polymorphonuclear cell function in vitro.[J]. British journal of clinical pharmacology, 1993, 35 3: 235-242. DOI: 10.1111/j.1365-2125.1993.tb05690.x
[4] A BONABELLO. Dexibuprofen (S+-isomer ibuprofen) reduces gastric damage and improves analgesic and antiinflammatory effects in rodents.[J]. Anesthesia and analgesia, 2003, 97 2: 402-408. DOI: 10.1213/01.ane.0000073349.04610.42