Modulation of oral drug bioavailability: from preclinical mechanism to therapeutic application

Area of Science:

• Pharmacology
• Oncology
• Drug Development

Background:

• Increasing development of oral anticancer drugs necessitates understanding factors limiting oral bioavailability.
• ATP-binding cassette (ABC) transporters and cytochrome P450 enzymes are key factors affecting oral drug absorption.

Purpose of the Study:

• To review the role of ABC transporters in limiting oral anticancer drug bioavailability.
• To discuss tissue distribution, physiological functions, tumor expression, and polymorphisms of ABC transporters.
• To explore drugs that inhibit ABC transporter function and their impact on anticancer pharmacokinetics.

Main Methods:

• Literature review on ABC transporters and their role in anticancer drug pharmacokinetics.
• Discussion of physiological functions, tissue distribution, and tumor expression of ABC transporters.
• Analysis of drug interactions and clinical examples of modulating ABC transporter activity.

Main Results:

• ABC transporters significantly limit oral bioavailability of anticancer agents.
• Polymorphisms in ABC transporters can influence drug efficacy and toxicity.
• Inhibiting ABC transporters, such as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), can enhance oral drug absorption.

Conclusions:

• Modulating ABC transporter activity is a viable strategy to improve oral anticancer drug bioavailability.
• Clinical examples demonstrate successful enhancement of oral drug absorption through coadministration with transporter inhibitors.
• Targeting ABC transporters holds promise for optimizing oral chemotherapy regimens.