The Evergreening of Biopharmaceuticals: Time to Defoliate

  title={The Evergreening of Biopharmaceuticals: Time to Defoliate},
  author={David F Lehmann and Sarabeth Wojnowicz},
  journal={The Journal of Clinical Pharmacology},
As a successful product approaches its date of patent expiration, chiral switching, that is, the isolation, testing, approval, and marketing of the pharmacologically active stereoselective isomer (enantiomer), termed “evergreening,” allows the manufacturer to maintain market share via exclusivity.1 The marketing of one stereoisomer typically emphasizes a single pharmacometric difference between the active and inactive enantiomer via extrapolation to the bedside.2 On rare occasions, eg, S… 
2 Citations

Lifetime evolution of ADHD treatment

A naturalistic review to review and comment on the available literature of ADHD treatment across the lifespan finds stimulants are endowed of a prompt efficacy and safety, whilst non-stimulants are useful when a substance abuse history is detected.

ADHD With Comorbid Bipolar Disorders: A Systematic Review of Neurobiological, Clinical And Pharmacological Aspects Across The Lifespan.

A systematic review of the scientific literature on the neurobiological, clinical features and current pharmacological management of ADHD comorbid with BDs across the entire lifespan, with a major focus on the adulthood.



Escitalopram: Superior to Citalopram or a Chiral Chimera?

The manufacturer’s claims of superiority for escitalopram over citaloprams are unwarranted, and the Swedish and Danish drug regulatory authorities reached similar conclusions.

Contrasting properties of albuterol stereoisomers.

  • C. PageJ. Morley
  • Biology, Medicine
    The Journal of allergy and clinical immunology
  • 1999

Enantiomers of bronchodilating beta2-adrenoceptor agonists: is there a cause for concern?

  • B. Waldeck
  • Medicine, Biology
    The Journal of allergy and clinical immunology
  • 1999

Putting chirality to work: the strategy of chiral switches

Most of the new drugs reaching the market today are single enantiomers, rather than the racemic mixtures that dominated up to ten years ago, but there are also important examples of new single-enantiomer drugs derived from 'chiral switches' of established racemates.

Preferential pulmonary retention of (S)-albuterol after inhalation of racemic albuterol.

Pre preferential retention of the (S)- compared with the (R)-enantiomer in the lung could lead to accumulation of the(S) enantiomer after long-term use of racemic albuterol.

The Seduction of Biomarkers in the Practice of Medicine and the Tyranny of Power in the Drug Approval Process: Lessons From Niacin

Niacin’s lack of impact on clinically relevant cardiovascular outcomes in this clinical trial, despite improvement in both surrogate biomarkers, is consistent with and extends observations from previous reports of the lack of benefit on cardiovascular outcomes when fenofibrate is added to simvastatin, despite a significant reduction in triglycerides.

Chiral switches

Escitalopram block of hERG potassium channels

Results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

Citalopram and cardiac toxicity

A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors forQT effects.