The marketing authorisation holder of terodiline is to be commended for the speed and the willingness with which it withdraw the drug as soon as it became evident that the risk is unlikely to be immediately manageable. Unfortunately, it did not follow up the recommendation from the regulatory assessor to investigate separately the two enantiomers systematically for their pharmacology, and possibly develop one of these if it can be shown to be devoid of potassium channel blocking activity while retaining a beneficial therapeutic effect. In light of the subsequent investigations, it seems possible that (—)-(S)-terodiline may have a favourable risk-benefit ratio. At the time of its withdrawal in 1991, the development of a single enantiomer may have appeared a tedious and potentially unrewarding activity but this, paradoxically, has been one of the striking features of new drug development in the period 1994-2001. This trend has resulted in the development of (S)-ketoprofen, (S)-ofloxacin, (S)-omeprazole, (R)-salbutamol, (S)-citalopram and (S)-ketamine among many others that are still in the pipeline (Shah, 2000). The other notable trend is the development of active but safer metabolites, such as fexofenadine, norcisapride, norastemizole and desmethyl-loratadine, all virtually devoid of the unwanted secondary cardiotoxic pharmacology or unwanted metabolic profile and drug interaction potential.
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