Stereoisomers ibuprofen

Ibuprofen is a popular analgesic and anti-inflammatory drug. There are two stereoisomeric forms of ibuprofen. This drug can exist as (S)- and (/ )-stereoisomers (enantiomers). Only the (5)-form is active. The (/ )-form is completely inactive, although it is slowly converted in the body to the active (5)-form. The drug marketed under the trade names, commercially known as Advil , Anadin , Arthrofen , Brufen , Nurofen , Nuprin , Motrin etc., is a racemic mixture of (/ )- and (5)-ibuprofen. 

An unique example of stereoisomer selective tissue uptake of stereoisomers is noted with NSAIDs. The R enantiomer of ibuprofen shows preferential uptake into fat following the administration of the racemate and individual isomersJ However, this apparent difference in fat distribution is probably a consequence of the selective metabolic uptake and formation of the coenzyme A thioester of the R isomer, which does not occur with the S isomer. 

Advances in industrial chemical processes have allowed pharmaceutical manufacturers to take drugs that were originally marketed in racemic form and divide them into individual enantiomers, each of which may have unique properties. For some drugs, such as zopiclone, only one enantiomer (eszopiclone) is active the FDA has allowed such once-generic drugs to be patented and marketed under another name. In other cases, such as ibuprofen, both enantiomers produce the same effects. Steroid receptor sites also show stereoisomer specificity. 

Many drug compounds are racemic mixtures of stereoisomers. In most cases, one of the isomers is more pharmacologically active than the other isomer, and each isomer may exhibit different pharmacokinetic properties. Warfarin, propranolol, verapamil, and ibuprofen are aU racemic mixtures of stereoisomers. Some drug interactions inhibit or increase the elimination of only one stereoisomer. The importance of the drug interaction depends on which isomer is affected. Other drugs, such as dextromethorphan, levofloxacin, and dUtiazem, are composed of just one stereoisomer. 

The natural conversion of an inactive stereoisomer to an active one is another case in which no a priori intention existed when the compound was synthesized. Ibuprofen is a good example. From a pharmacokinetic point of view, one may consider that the reversibly formed metabolite represents a compartment for the parent compound, and adequate provision must be taken when analyzing this type of data. 

The manufacture of fine chemicals, particularly drugs, fragrances, and flavors, is undergoing a major revolution now as a result of the capability of chemists to prepare these chemicals, mainly drugs, in their purest isomeric forms (as stereoisomers). This shift to pure forms has been described by Brown in the following words (1990) (see also Deutsch, 1991) A mixture of stereoisomers in a medicine will (now) need to be justified just the same way as any other mixture of compounds. Indeed, in the United States today (as in many other advanced countries), the use of pure enantiomeric forms is practically a requirement since extensive justification is needed to continue with racemates (FDA, 1992). As a consequence, the combined sales of the chiral top ten drugs (ammoxydllin, enalapril, ampicillin, captopril, pravastatine, diltiazem, ibuprofen, lovastatin, naproxen, and fluoxetine) in 1994 amounted to more than 16 billion dollars (Sheldon, 1996). (Of these, ibuprofen and fluoxetine are still sold as racemates.)... 

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