Prediction of the vitreal half-life of small molecular drug-like compounds

Pharm Res. 2012 Dec;29(12):3302-11. doi: 10.1007/s11095-012-0822-5. Epub 2012 Jul 10.

Abstract

Purpose: To build a fast, user-friendly computational model to predict the intravitreal half-lives of drug-like compounds.

Methods: We used multivariate analysis to build intravitreal half-life models using two data sets, one with experimental data derived from both pigmented and albino rabbits and another including only data from experiments with albino rabbits.

Results: The final models had a Q(2) value of 0.65 and 0.75 for the mixed and albino rabbit models, respectively. The models performed well in predicting the intravitreal half-life of an external test set. In addition, the models are physiologically interpretable, containing mainly hydrogen bonding and lipophilicity descriptors.

Conclusion: The developed models enable reliable predictions of intravitreal half-lives for use in the early drug development stages, without the need for prior experimental data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Retinal Barrier / metabolism
  • Computer Simulation
  • Half-Life
  • Hydrogen Bonding
  • Intravitreal Injections
  • Models, Biological
  • Multivariate Analysis
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / metabolism*
  • Rabbits
  • Vitreous Body / metabolism*

Substances

  • Pharmaceutical Preparations