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Updated: Jan 20, 2026

Nonlinear Pharmacokinetics: Role of Transporters
01:27

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How Transporters Have Changed Basic Pharmacokinetic Understanding.

Leslie Z Benet1, Christine M Bowman2, Jasleen K Sodhi2

  • 1Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine, University of California San Francisco, 533 Parnassus Avenue, Room U-68, UCSF Box 0912, San Francisco, California, 94143, USA. leslie.benet@ucsf.edu.

The AAPS Journal
|September 5, 2019
PubMed
Summary

Drug transporters significantly impact drug distribution volume, altering pharmacokinetic parameters like half-life. Dosing decisions should focus on clearance/bioavailability (CL/F) changes, not just half-life, due to transporter effects.

Keywords:
clearancehalf-lifemean residence timetransportersvolume of distribution

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Drug Transporter Science

Background:

  • Drug disposition principles are evolving with advancements in transporter research.
  • Transporter proteins play a crucial role in the absorption, distribution, metabolism, and excretion (ADME) of drugs.

Purpose of the Study:

  • To highlight the significant influence of drug transporters on the volume of distribution.
  • To explain how transporter-mediated effects can alter key pharmacokinetic parameters, including half-life.

Main Methods:

  • Review and analysis of existing literature on drug transporters and pharmacokinetics.
  • Examination of case studies illustrating transporter involvement in drug-drug interactions and pharmacogenomic variations.

Main Results:

  • Transporter involvement in drug interactions can alter volume of distribution, leading to non-intuitive changes in half-life.
  • Unlike metabolic interactions, transporter effects can cause decreases in both clearance and half-life simultaneously.
  • Volume of distribution changes significantly influence pharmacokinetic outcomes.

Conclusions:

  • Drug dosing strategies must account for transporter-mediated alterations in volume of distribution.
  • Clearance divided by bioavailability (CL/F) is a more reliable metric for dosing adjustments than half-life alone.
  • Understanding transporter roles is critical for accurate pharmacokinetic predictions and personalized medicine.