Antedrugs: an approach to safer drugs

Curr Med Chem. 2005;12(19):2227-39. doi: 10.2174/0929867054864840.


The antedrug concept was introduced by Lee and Soliman in 1982 in designing potent, yet safer locally active anti-inflammatory steroids. Antedrug is defined as an active synthetic derivative that is designed to undergo biotransformation to the readily excretable inactive form upon entry in the systemic circulation. Thus, are minimizing systemic side effects and are increasing the therapeutic indices. Steroid-21-oate esters have been developed as the first of this kind, which quickly hydrolyzed to the corresponding inactive steroid acids thereby exerting minimal systemic side effects. Later, other steroidal and nonsteroidal antedrugs have also been developed. The cost, complexity and length in development of a new therapeutic drug, in addition to the adverse drug reactions, the potential risk factors causing the withdrawal of the drugs from the market, have made the approach of antedrug design unique and attractive to the scientists involved in drug design. Considering these factors, the concept which strictly designed to eliminate the deleterious adverse systemic effects, is becoming an affordable approach in drug development arena. This review is not intended to be comprehensive; instead the focus will be on the recent advances in steroidal as well as nonsteroidal antedrugs, which appear to offer new leverage to the development of safer and more efficacious therapeutic agents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems*
  • Amides / chemistry
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biotransformation
  • Drug Utilization Review*
  • Esters / chemistry
  • Glucocorticoids / chemistry
  • Glucocorticoids / pharmacology
  • Humans
  • Prodrugs / adverse effects
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Risk Factors
  • Safety
  • Steroids / chemistry
  • Steroids / pharmacology


  • Amides
  • Anti-Inflammatory Agents
  • Esters
  • Glucocorticoids
  • Prodrugs
  • Steroids