How Transporters Have Changed Basic Pharmacokinetic Understanding

The emergence and continued evolution of the transporter field has caused re-evaluation and refinement of the original principles surrounding drug disposition. In this paper, we emphasize the impact that transporters can have on volume of distribution and how this can affect the other major pharmacokinetic parameters. When metabolic drug-drug interactions or pharmacogenomic variance changes the metabolism of a drug, the volume of distribution appears to be unchanged while clearance, bioavailability, and half-life are changed. When transporters are involved in the drug-drug interactions or pharmacogenomic variance, the volume of distribution can be markedly affected causing counterintuitive changes in half-life. Cases are examined where a volume of distribution change is significant enough that although clearance decreases, half-life decreases. Thus, drug dosing decisions must be made based on CL/F changes, not half-life changes, as such volume of distribution alterations will also influence the half-life results.