Ketoprofen activity

Benzoyl-2,3-dihydro-lH-pyrrolizine-l-cai boxylic acid (ketorolac, L ) and 2-(3-benzoyl-phenyl)propionic acid (ketoprofen, L ) ai e biologically activ ligands used in medicine as non-steroidal anti-inflammatory dmgs. 

N. Dubois-Presle, F. Lapicque M. H. Maurice, S. Fournel-Gigleux, J. Magdalou, M. Abiteboul, G. Siest, P. Netter, Stereoselective Esterase Activity of Human Serum Albumin toward Ketoprofen Glucuronide , Mol. Pharmacol. 1995, 47, 647 - 653. 

This series of anti-inflammatory, analgesic, and fever-reducing compounds (ibuprofen, naproxene, ketoprofen, fenprofen) can be equally identified as both propionic acid derivatives as well as phenylpropionic acid derivatives. The mechanism of their action is not conclusively known however, it has been suggested that it is also connected with the suppression of prostaglandin synthetase activity. 

Supercritical fluid extraction is a potential technique for the purification of pharmaceutical products containing residual solvents. The solubilities of three inhibitors of inflammatory activity, Ketoprofen, Piroxicam, and Nimesulide, in supercritical CO2, measured using a dynamic saturation technique, were reported at pressures between 100 bar and 220 bar and at two temperatures 312.5 K and 331.5 K. The solubilities exhibit a clear dependence on the solvent density, and this has been used to provide a simple and precise correlation of the data (Macnaughton et al., 1996). 

Ketoprofen (2-(3-benzoylphenyl)propionic acid), one of the most active non-steroidal antiinflammatory drugs, is employed in the long-term treatment of rheumatoid arthritis and also as an analgesic in the treatment of pain of varying origins [1]. Clinical use, however, requires a dose schedule of 100-200 mg 3-4 times a day, the duration of action of a single oral dose being only 6-8 h [2]. 

Ketoprofen is usually given as the racemate, the pharmacological action being mainly carried out by the S(+)-enantiomer. The active enantiomer is available in some countries since 1997 as the trometamol salt, which is said to be absorbed more quickly thus leading to an earlier onset of action. 

A very large number of copper compounds have been tested for antiinflammatory activity, and various copper complexes of antiarthritic drugs have been found to be more effective than the parent drugs alone (including aspirin, D-penicillamine, ketoprofen and gold thiomalate).25... 

Ketoprofen (S)-( +) enantiomer is analgesic/ anti-inflammatory, R-(-) isomer active against bone loss in periodontal disease 176... 

There are very few data on the gastrointestinal toxicity of over-the-counter doses of ketoprofen. In an endoscopic short-term study in healthy subjects ketoprofen was associated with significant gastrointestinal toxicity (9). Another endoscopic study showed that the i -enantiomer of ketoprofen has less gastrointestinal toxicity than the racemic mixture or the 5-enantiomer while retaining good analgesic activity (SEDA-22,116). 

There is limited evidence that a few NSAIDs, such as meclofenamic acid and ketoprofen, have some inhibitory effects on lipoxygenase. For example, meclofenamic acid has been shown to inhibit 5-lipoxygenase and 15-lipoxygenase activities in... 

The mechanisms of action of ketoprofen have not been definitively proven in the horse, although ketoprofen has been shown to inhibit COX enzymes. Several studies carried out in horses have shown that ketoprofen, administered at doses that significantly inhibited PG production, had no effect on LT production (Landoni Lees 1995a, Owens et al 1995a) and, therefore, appears not to have any significant effect on lipoxygenase activity. 

Vedaprofen is a propionic acid derivative that, like carprofen and ketoprofen, exists as two enantiomers with different pharmacokinetic profiles in the horse. For example, the plasma disposition of S(-t-)-vedaprofen is characterized by a very rapid decline with a plasma half-life of less than 1 h while R(-)-vedaprofen has a more prolonged elimination phase with a plasma half-life of over 2h (Lees et al 1999). Both enantiomers also accumulate in and exhibit a delayed elimination from inflammatory exudates. In horses, vedaprofen appears to be slightly selective for the COXl enzyme. For example, the median effective concentration for inhibition of serum TXB2 production, which is assumed to be a reflection of COXl activity, was much lower than that for inhibition of inflammatory infiltrate PGE2 production, which is assumed to be a reflection of COX2 activity. Although the results of these studies are promising, there are no published data on the clinical effectiveness and safety of vedaprofen in horses. 

Examples of chiral CE separations of racemic drugs are the following. (/ )-(-)-ketoprofen has successfully been separated from ketoprofen and detected (Fig. 4).f (5)-(+)-ketoprofen is the active component. Also, simultaneous chiral separation of a basic drug compound, 2(/ )-A-[l-(6-amino-pyridin-2-ylmethyl) pip-eridin-4-yl]-2-[(l/ )-3,3-difluorocyclopentyl]-2-hydroxy-2-phenyl-acetamide, and its chiral acidic intermediate, (/ ,/ ) l-(2,2-difluorocyclopentyl)-phenylacetic acid, has been achieved by CE using a single-isomer CD, octakis (2,3-diacetyl-6-sulfo)-y-CD (ODAS-y-CD).P l Carnitine has been separated using 50 mM DM-p-CD in 20 mM phosphate buffer (pH 4.3) as chiral selector. The separations are done at 30° C in a fused-silica capillary, dynamically coated with triethanolamine present in the background electrolytes. 

Cross-linked crystals of lipase from Candida rugosa (CRL) were applied in the resolution of racemic ketoprofen chloroethyl ester. In batch-wise operation, the half-life of the catalyst was reached after about 18 cycles or, in terms of enzyme consumption, about 5.6 g of enzyme protein were consumed to prepare 1 kg of (S)-ketoprofen. CRL suffers from a low specific activity towards this poorly water-soluble substrate which may explain the high enzyme input [117]. 

All compounds of the test dataset are nonsteroidal anti-inflammatory drugs (NSAIDs) and are thus relatively similar in terms of their pharmacological properties (Fig. 18). The compounds are 1, acetylsalicylic acid 2, diclofenac 3, flufe-namic acid 4, flubiprofen 5, ibuprofen 6, indometacin 7, ketoprofen 8, meclofe-namic acid 9, mefenamic acid 10, naproxen 11, piroxicam 12, sulindac sulfide (active metabolite of sulindac) 13, tenoxicam 14, meloxicam 15, cgp 28238 16, DuP-697 17, L-745-337 18, 6-methoxy-2-naphthylacetic acid (active metabolite of nabumeton) 19, NS-389 20, SC 58125. 

---