To the average consumer, fexofenadine, or better known by its brand name, Telfast, is a non-sedating anti-allergy medication that can help to stop itches and runny noses. Fexofenadine is an over-the-counter medication that does not require frequent monitoring or dose titration. It is thus surprising to find that there are 22 papers related to fexofenadine population pharmacokinetics on PubMed.

Turns out, fexofenadine is really useful for measuring drug transporter activity as its drug exposure is very sensitive to changes in the function of these transporters (e.g. OATP1B1 and P-gp). These are referred to as probe substrates in literature, and are often used as a proxy to study the impact loss of transporter function might make to other drugs cleared by similar transporter pathways. Furthermore, a healthy person can take fexofenadine without experiencing severe side effects, allowing it to be used safely in clinical trials.

In this paper by Frédéric Gaspar et al. https://pubmed.ncbi.nlm.nih.gov/39798016/, they precisely do just that to study how drugs cleared by P-gp may be impacted in older adults alongside impaired renal function and concomitant medications that inhibit P-gp.  Previously, most of these studies have been done in healthy volunteers who are younger. They found that age, renal function and P-gp inhibitors all contribute to an increase in fexofenadine concentrations, suggesting that clinicians should pay closer attention to drugs that are P-gp substrates in older adults, especially those with reduced renal function. Interestingly, only 10% of fexofenadine is cleared by the kidneys. Furthermore, two-thirds of the study population had reduced P-gp activity even without P-gp inhibitors, suggesting a potential link between reduced kidney function and P-gp activity that might contribute to this decreased drug clearance. This is another nice study that clearly applies useful pharmacological concepts of using a probe drug to understand drug disposition better. Hope you learnt something with me!