Section 2 The optical isomers of ibuprofen

Summary

Because ibuprofen possesses an asymmetric carbon atom, it occurs as a dextro (+) or laevo (-) isomer. The purpose of this study was to determine the contribution made by each isomer to the activity of the normal racemic mixture.

A number of in vivo pharmacological tests were carried out in three different animal species, namely guinea pigs, rats and mice, to compare the potencies of the dextro, laevo and racemic mixture forms. All three forms proved to be very similar in potency in the anti-inflammatory and analgesic models used. However, when the compounds were examined in vitro for their ability to inhibit a bovine seminal vesicle microsomal preparation of prostaglandin synthetase, it was found that almost all the activity resided in the dextro isomer. The ID₅₀ levels (50 % inhibitory dose) are given in Table I.

Table I. 1D₅₀ levels of three different forms of ibuprofen in a bovine seminal vesicle microsomal preparation of prostaglandin synthetase

Some workers have claimed that the anti-inflammatory activity of certain 2-phenylpropionic acids resides almost entirely in the dextro isomer. The results of this study on the inhibition of prostaglandin synthetase in vitro might suggest that this is also true for ibuprofen, but little difference in pharmacological activity in vivo was seen, in fact, between the isomers. This implies that the conversion of the laevo to the dextro form takes place in the animal body, and explains a very early observation from these laboratories that, in man, urinary metabolites of ibuprofen are dextro-rotatory.