R -ketoprofen

It has been reported that the clearance of both isomers of ketoprofen glucurcHTiide, the main metabolite of ketoprofen, another racemic profen, is reduced in elderly arthritic patients due, perhaps to an age-induced reduced renal function (17). As the therapeutic benefits of this drug are ascribed mainly to its S enantiomer and R-ketoprofen is not inverted to a... 

It is known that there are several long-chain acyl-Coenzyme A synthetases (ACS). ACSl shares some similar catalytic and antigenic properties to pahnitoyl-CoA synthetase [29]. Nevertheless, there is evidence of multiple forms of microsomal coenzyme A ligase catalyzing the formation of 2-APA CoA thioesters with several binding sites as well as a catalytic site. For instance, R-ketoprofen CoA appears to be catalyzed by an alternative isoform of a microsomal CoA ligase that is not shared by fenoprofen and ibuprofen [30,31]. 

Gabor F, Ertl B, Wirth M, Mallinger R. Ketoprofen-poly(D,L-lactic-co-glycolic add) microsphetes Influence of manufacturing parameters and type of polymer on the release characteristics. Journal of Microencapsulation. January-February 1999 16(1) 1-12. PubMed PMID 9972498. 

Ketoprofen, or 2-(3-benzoylphenyl)propionic acid, is a kind of 2-arylpropionic acid that represents an important group of nonsteroidal anti-inflammatory drugs (NSAIDs), and is widely used to relieve inflammation and pain resulting from arthritis, sunburn, menstrual pain, or fever. Previous studies have shown that its anti-inflammatory activity lies mainly in its (S)-enantiomer, while its (i )-enantiomer is a potentially highly potent analgesic treatment for neuropathie pain. Therefore, it is very valuable to obtain optically pure (S)- or (R)-ketoprofen. 

Figure 6 Minimum energy conformers of the interaction of / (—)-carvone with R(—)-ketoprofen (14) if(—)-carvone with 5(+)-ketoprofen (15) and 5(+)-carvone with either R- or 5-ketoprofen (16). (From Ref. 121.)...

Electropherograms of a urine sample (8 ml) spiked with non-steroidal anti-inflammatory drugs (10 p-g/ml each) after direct CE analysis (b) and at-line SPE-CE (c). Peak identification is as follows I, ibuprofen N, naproxen K, ketoprofen P, flurbiprofen. Reprinted from Journal of Chromatography, 6 719, J. R. Veraait et al., At-line solid-phase exti action for capillary electrophoresis application to negatively charged solutes, pp. 199-208, copyright 1998, with permission from Elsevier Science. 

Pehourcq, R, Jarry, C., and Bannwarth, B., Chiral resolution of flurbiprofen and ketoprofen enantiomers by HPLC on a glycopeptide-type column chiral stationary phase, Biomed. Chromatogr, 15, 217, 2001. 

Tixier C., H.P. Singer, S. OUers, and S.R. Muller (2003). Occurrence and fate of carbamaze-pine, clorolibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface water. Environmental Science and Technology 37 1061-1068. 

The use of cellulose ethers in producing matrix-type sustained release tablets is well documented [7]. Hydrophilic matrices of ketoprofen with hydroxypropylmethylcellulose (KET-R)... 

Fig. 1—Release profile of ketoprofen from tablet KET-R basket 50 rev/min pH 1.2.

The release curve of ketoprofen obtained from the KET-R tablet at pH 1.2 and 50 rev/min is shown in Fig. 1. The release profile was zero order up to 90% drug content. The equation obtained by plotting the percentage released vs. time was y=0.187x-1.997, 0.99. No burst effect was present. 

The effect of basket rotation rate and pH on the release profile of ketoprofen from the KET-R tablet is presented in Fig. 2. The release rate of ketoprofen from the system increased with increasing basket rotation rate and changed from 11%/h at 50 rev/min to 16%/h at 150 rev/min, but the profile remained linear up to 80% drug content. Moreover, the drug release profile at pH 6. 8 (y=0.189x-1.091, r= 0.99) was very similar to that at pH 1.2 and thus the ketoprofen released... 

Precirol was successf ully used as a retardant in matrix tablet formulations [8]. The effect of Precirol incorporation into the hydroxypropylmethylcellulose matrix tablets was therefore investigated. Precirol drug ratios of 1 3, 1 2 and 1 1 were used (tablets KET-R A, B, and C). No significant differences in the volume decrease profiles of glassy cores and in ketoprofen release profiles (Fig. 4) in comparison with original core were obtained, even with increased Precirol. 

The release profile of ketoprofen from the 2/3 CAP coated core (KET-R CAP tablet) was of zero order (y=0.037x-1.263, r=0.99) and the drug release rate was clearly lower than the original core, as is shown in Fig. 5. However, the technique of preparation of KET-R CAP tablets was somewhat complex, requiring considerable accuracy in the partial coating phase, and not easily applicable on an industrial scale. 

Fig. 4—Release profile of ketoprofen from tablets containing Precirol (50 rev/min pH 1.2) tablet KET-R . tablet KET-R A . tablet KET-R B , tablet KET-R C.

The ketoprofen release profiles from these tablets are shown in Fig. 6. The release curves were linear (r=0.99) and the release rate appeared to decrease with increasing coating amounts. On the basis of the linear inverse relation found between the drug release rate and the coat (Fig. 7), the release rate can be varied with predictable effects by varying the coating amount. In particular the KET-R 15 tablet showed a lower rate of drug release than the 2/3 CAP coated tablet (0.96%/h... 

Meharg, A.A., Taggart, M.A., Venter, L. and Cuthbert, R. (2009) Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures a new threat from ketoprofen. Biol. Lett., 6 (3), 339-341. 

Jamali, F., Brocks, D.R. Clinical pharmacokinetics of ketoprofen and its enantiomers. Clin. Pharmacokinet. 1990, 19, 197-217. 

Table 2 gives chromatographic data for different classes of enantiomeric dmgs resolved by P-CD bonded phases (8). Drugs for which resolution factors (R) greater than 1.0 were obtained include mephenytoin, ketoprofen, chlorpheniramine, and the barbiturates mephobarbital and hexobarbital. Cyclodextrin-bonded phases provide a rapid and specific technique for the pharmacological evaluation of racemic dmgs. 

Sheng, J. J., N. A. Kasim, R. Chandrasekharan, and G. L. Amidon. 2006. Solubilization and dissolution of insoluble weak acid, ketoprofen Effects of pH combined with surfactSnt. J. Pharm. Sci. 29 306-314. 

FIGURE 8 Effect of buffer (ionic) strength on enantioresolution of (a) enantiomers of C6H5C0NHCHRC02H, where R is ( ) -CH2OH, ( ) -CH3 and ( ) -CH3 on the BSA-based CSP, (b) iV-benzoyl alanine on BSA-based CSP, and (c) ketoprofen on avidin CSP with phosphate buffer as the main component of the mobile phases in all of the studies. (From Refs. 28, 32, and 70.)... 

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

Abad, S., Bosca, F., Domingo, L.R., Gil, S., Pischel, U., and Miranda, M.A. (2007) Triplet reactivity and regio-/stereo-selectivity in the macrocydization of diastereomeric ketoprofen-quencher conjugates via remote hydrogen abstractions. Journal of the American Chemical Society, 129, 7407—7420. 

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