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Do prodrugs deliver?

Dennis A Smith1

  • 1Sandwich Laboratories, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK. dennis.a.smith@pfizer.com

Current Opinion in Drug Discovery & Development
|September 6, 2007
PubMed
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This review explores prodrug strategies for enhancing drug delivery and therapeutic outcomes. Understanding pharmacokinetic/pharmacodynamic models and polar surface area is crucial for successful prodrug design and oral absorption.

Area of Science:

  • Pharmacology
  • Drug Delivery
  • Medicinal Chemistry

Background:

  • Prodrugs are modified drug forms used to improve pharmacokinetic properties.
  • Conventional prodrugs aim to increase systemic drug concentrations, often enhancing oral absorption.
  • Targeted prodrugs are designed to improve the therapeutic ratio by directing drugs to specific sites.

Purpose of the Study:

  • To review the prodrug concept, encompassing both conventional and targeted approaches.
  • To emphasize the importance of pharmacokinetic/pharmacodynamic modeling in prodrug development.
  • To highlight the role of polar surface area in predicting oral absorption and drug efficacy.

Main Methods:

  • Literature review of prodrug strategies and their applications.
  • Analysis of pharmacokinetic/pharmacodynamic principles relevant to prodrugs.

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  • Discussion of physicochemical properties, such as polar surface area, influencing drug absorption and targeting.

    • Main Results:

    • Conventional prodrugs primarily focus on improving oral bioavailability.
    • Targeted prodrugs aim to enhance efficacy and reduce off-target toxicity.
    • Pharmacokinetic/pharmacodynamic modeling is essential for overcoming delivery barriers.
    • Polar surface area is a key predictor for oral absorption suitability and on-site drug retention.

    Conclusions:

    • Successful prodrug design requires a thorough understanding of drug disposition and action.
    • Pharmacokinetic/pharmacodynamic modeling provides a framework for optimizing prodrug strategies.
    • Physicochemical properties like polar surface area are critical for rational prodrug development, particularly for oral administration.