Prodrugs pp 429-445 | Cite as

Targeting - Theoretical and Computational Models

  • Roger A. Rajewski
  • Michelle P. McIntosh
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume V)


Prodrugs are pharmacologically inactive compounds that undergo an in vivo chemical or enzymatic conversion to an active drug molecule to produce a therapeutic effect. An emerging application for prodrug technologies is their use for targeting drugs to specific tissues or cell types. The focus of this chapter is to review the potential use of prodrug technologies in achieving site-specific targeted delivery of drugs and to use computational models to illustrate conditions under which the targeted delivery can be achieved.


Target Site Central Volume Drug Permeability Drug Input Target Delivery System 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Box GEP. Robustness in the Strategy of Scientific Model Building. In: Launer RL and Wilkinson GN. Robustness in Statistics. New York, NY. Academic Press; 1979:201–236Google Scholar
  2. Ettmayer P, Amidon GL, Clement B, and Testa B. Lessons Learned from Marketed and Investigational Prodrugs, J Med Chem 2004; 47:2393–2404PubMedCrossRefGoogle Scholar
  3. Han HK and Amidon GL. Targeted Prodrug Design to Optimize Drug Delivery. AAPS PharmSci 2000; 2(1) article 6Google Scholar
  4. Hunt CA, MacGregor RD, and Siegel RA. Engineering Targeted In Vivo Drug Delivery. I. The Physiological and Physiochemical Principles Governing Opportunities and Limitations. Pharm Res 1986; 3:333–344CrossRefGoogle Scholar
  5. Kearney AS. Prodrugs and Targeted Drug Delivery. Adv Drug Deliv Rev 1996; 19:225–239CrossRefGoogle Scholar
  6. Rowland M and McLachlan A. Pharmacokinetic Considerations of Regional Administration and Drug Targeting: Influence of Site of Input in Target Tissue and Flux of Binding Protein. J Pharmacokinet Biopharm. 1996; 24:369–387PubMedCrossRefGoogle Scholar
  7. Stella VJ and Himmelstein KJ. Prodrugs and Site-Specific Drug Delivery. J Med Chem 1980; 23:1275–1282.PubMedCrossRefGoogle Scholar
  8. Stella VJ and Himmelstein KJ. Critique of Prodrugs and Site-Specific Drug Delivery. In: Bundgaard H, Hansen AB and Kofod, H. Optimization of Drug Delivery. Munksgaard, Copenhagen; 1982:134–155Google Scholar
  9. Stella VJ and Himmelstein KJ. Prodrugs: A Chemical Approach to Targeted Drug Delivery. In: Borchardt RT, Repta AJ, and Stella VJ. Directed Drug Delivery. Clifton, NJ: Humana Press; 1985a:247–267Google Scholar
  10. Stella VJ and Himmelstein KJ. Site-Specific Drug Delivery via Prodrugs. In: Bundgaard H. Design of Prodrugs. Amsterdam: Elsevier Science Publishers BV; 1985b:177–198Google Scholar
  11. Suzuki H, Nakai D, Takeshi S, and Sugiyama Y. Design of a Drug Delivery System for Targeting Based on Pharmacokinetic Considerations. Adv Drug Deliv Rev 1996; 19:335–357CrossRefGoogle Scholar
  12. Yuan F, Baxter LT, and Jain RK. Pharmacokinetic Analysis of Two-Step Approaches using Bifunctional and Enzyme-Conjugated Antibodies. Cancer Res 1991;51:3119–3130.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Roger A. Rajewski
    • 1
  • Michelle P. McIntosh
    • 1
  1. 1.Center for Drug Delivery ResearchThe University of KansasLawrenceUSA

Personalised recommendations