Absolute Configuration and Racemic Switch

Fexofenadine is rapidly absorbed and has a long duration of action, making it suitable for once daily administration, and it provides a more improved quality of life than any other antiallergic drug [6-8]. 

Pharmacokinetic parameters observed for fexofenadine enantiomers are comparable except for the area under the curve (AUC) for plasma concentrations (Table 10.2) [9]. 

In a detailed clinical study, it was demonstrated that both enantiomers of fexofenadine possess equal potency but differ in selected pharmacokinetic parameters [10]. A 63 37 steady-state ratio of f -(-f)-l and 5-(—)-l was observed in plasma and this remained constant across time and dosing. In a later study, it was found that the AUC and the maximum plasma concentration (Cmax) of f -(-f)-l were significantly greater than those of the 5-(—)-enantiomer [11]. Furthermore, plasma and renal clearance of oral 5-(—)-fexofenadine were both significantly greater than for the f -(-i-)-enantiomer. 

All these studies of non-racemic fexofenadine were prompted by the development of an HPLC method for the chiral separation of fexofenadine enantiomers in human plasma [11, 12]. Based on these and additional studies on the pharmacokinetic [13] and enantioselective disposition of fexofenadine in the presence of verapamil [14], 

A racemic switch , that is, replacement of racemic fexofenadine on the market by the f -(+)-enantiomer, is not likely, however, since the cost-benefit considerations are unfavourable due to the relatively minor positive therapeutic effect and the considerably higher production costs of the pure / -(+)-enantiomer. Nevertheless, because of the exciting enantioselective syntheses and stereochemical properties of the enantiomers of fexofenadine, these will be considered in the next section. 

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