title: Incorporation of in silico biodegradability screening in early drug development--a feasible approach?
abstract: BACKGROUND
  The concentration of a pharmaceutical found in the environment is determined by the amount used by the patient, the excretion and metabolism pattern, and eventually by its persistence. Biological degradation or persistence of a pharmaceutical is experimentally tested rather late in the development of a pharmaceutical, often shortly before submission of the dossier to regulatory authorities.
  
  
  METHODS
  To investigate whether the aspect of persistence of a compound could be assessed early during drug development, we investigated whether biodegradation of pharmaceuticals could be predicted with the help of in silico tools. To assess the value of in silico prediction, we collected results for the OECD 301 degradation test ("ready biodegradability") of 42 drugs or drug synthesis intermediates and compared them to the prediction of the in silico tool BIOWIN.
  
  
  CONCLUSIONS
  Of these compounds, 38 were predictable with BIOWIN, which is a module of the Estimation Programs Interface (EPI) Suite™ provided by the US EPA. The program failed to predict the two drugs which proved to be readily biodegradable in the degradation tests. On the other hand, BIOWIN predicted two compounds to be readily biodegradable which, however, proved to be persistent in the test setting.
  
  
  CONCLUSIONS
  The comparison of experimental data with the predicted one resulted in a specificity of 94% and a sensitivity of 0%. The results of this study do not indicate that application of the biodegradation prediction tool BIOWIN is a feasible approach to assess the ready biodegradability during early drug development.
authors.affiliation: Toxicology, Bayer Schering Pharma, 13353, Berlin, Germany. thomas.steger-hartmann@bayer.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Steger-Hartmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Länge
authors.forename: Klaus
authors.initials: K
authors.lastname: Heuck
mesh_terms: D001673:Biodegradation, Environmental; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005240:Feasibility Studies; D055772:Green Chemistry Technology / Q000379:methods*; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations