The COVID-19 pandemic, coupled with ongoing challenges in the development of effective anticancer therapies, has underscored critical limitations in the traditional understanding of bioavailability. Historically, the concept of bioavailability has been narrowly defined, focusing primarily on systemic absorption and the subsequent distribution of drugs to tissues. However, this perspective fails to account for the complexities of how drugs interact with specific intracellular targets. In this letter to the editor, we advocate for the introduction of a more comprehensive definition of bioavailability, one that considers not only the absorption and tissue access of a drug but also the speed and extent to which a biologically active molecule reaches its intended intracellular site of action.

We propose that, in addition to absorption, other key factors such as protein binding, cellular penetration, metabolic stability, and the activity of efflux pumps should be incorporated into the bioavailability framework. These factors play a pivotal role in determining drug efficacy, particularly in the treatment of intracellular infections or disorders involving specific cellular targets. By expanding the definition of bioavailability in this way, we can better address the challenges of drug development and enhance the precision of therapeutic interventions that require targeted intracellular delivery. delivery.