I Ibuprofen

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. 

In a comparable system, (I ,S)-ibuprofen can be separated by a membrane reactor [83], see Fig. 13.10. The technique comprises a stereo-specific hydrolysis by an enzyme. Subsequently, the enantiomeric ester is extracted into the organic phase on the other side of the membrane. In the system developed by Sepracor Inc., (i )-ibuprofen is selectively hydrolyzed by proteases in a hollow-fiber unit and the (S)-ibuprofen ester can be isolated at 100% yield. This configuration also applies for enantioseparation of other acids such as naproxen and 2-chloropropionic acid. 

Caro H, Conture B, Pethilaz R, Royar JC. Etude clinique sur I ibuprofen sous forme suppositoires. Gaz Med Fr... 

In a systematic review of comparisons of Saridon (propyphenazone 150 mg + paracetamol 250 mg -I- caffeine 50 mg), paracetamol 500 mg + aspirin 500 mg -I-ibuprofen 200 mg, and placebo in 500 healthy adults, of whom 329 (66%) had moderate and 171 (34%) severe acute dentoalveolar pain, more of the patients who received Saridon reported pain gone/partly gone and fewer reported pain unchanged or worse at 30 and 60 minutes (1). There were adverse events in 20 patients (4.0%), with no significant differences between the groups. The most common adverse events were gastrointestinal disorders, followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac, and general disorders. 

Two prospective, crossover, placebo controlled, double-bhnd evaluations of the nephroprotective role of misoprostol in patients with mild stable chronic renal failure, taking either ibuprofen or indomethacin have been reported [183]. The mean baseline GFR of the patients at the time of entry into the study was 53 ml/min (misoprostol)/55 ml/min (placebo), and 57 ml/min (misoprostol)/57 ml/min (placebo) in Study I (ibuprofen) and Study II (indomethacin) respectively. At this level of renal functional impairment, the use of the non-selective NSAIDs did not produce additional significant impairment of renal function, hence a renal protective role for misoprostol could not be... 

Not only is it chemically wasteful to synthesize and administer an enantiomer that does not serve the intended purpose, many examples are now known where the presence of the wrong enantiomer in a racemic mixture either affects the body s ability to utilize the right enantiomer or has unintended pharmacological effects of its own. The presence of (i )-ibuprofen in the racemic mixture, for instance, slows substantially the rate at which the S enantiomer takes effect in the body, from 12 minutes to 38 minutes. 

Whitlam JB, Crooks MJ, Brown KF and Pedersen PV, Binding of nonsteroidal antiinflammatory agents to proteins I. Ibuprofen-serum albumin interaction, Biochem. Pharmacol., 28,675-678 (1979). NB The pJCa was determined by die solubility technique of Albert and Serjeant (1971) to be 4.13 0.05. 

In addition, the lesser active (I )-ibuprofen enantiomer (experts called it the distomer, see Chapter 26) and a few... 

In 2006, another lipase-catalysed hydrolysis process under in situ racemisation of the remaining (i )-ibuprofen ester substrate with sodium hydroxide as... 

Generic Name hydrocodone + ibuprofen, oxycodone -I- ibuprofen... 

Sample Problem I Ibuprofen,Cj3Hjg02, is the active ingredient in many nonprescription pain relievers. 

It is well documented [12-16] that a certain proportion of i (—)-ibuprofen might undergo a metabolic inversion in vivo to the active 5(+) enantiomer, as depicted in Fig. 2. The inversion proceeds [17,18] via the stereoselective transformation of the R(—) isomer in the thioester with the coenzyme A, which can be partially teansesterified by endogenous triacylglycerols to be stored in the lipidic tissues as hybrid triglycerides. / -Ibuprofen-CoA is subsequently isomerized to S-ibuprofen-CoA, which is quickly hydrolyzed to ff 5(+)-ibuprofen. This process is irreversible, so that 5 (+)-ibuprofen is not stored in the lipidic tissue. Recently, the possible formation of an (R)-adenylate intermediate prior to the formation of the (R)-coenzyme thio ester has been described as the stereoselective step... 

---