Which of the following factors can lead to increased free drug concentration in the bloodstream?

The correct answer highlights how aging impacts drug pharmacokinetics, particularly in relation to protein binding and distribution. As individuals age, several physiological changes occur, including decreased liver and renal function, alterations in body composition, and changes in protein levels, particularly albumin. These shifts can reduce the binding sites available for highly protein-bound drugs, resulting in an increased concentration of free (unbound) drug in the bloodstream.

This phenomenon is crucial because the unbound drug is typically the active form that exerts pharmacological effects, leading to a potential increase in drug efficacy and, potentially, toxicity. Therefore, as aging progresses and these physiological changes become pronounced, the overall drug metabolism and clearance mechanisms are impaired, which can lead to a higher free drug concentration.

The incorrect options pertain to factors that either do not specifically increase free drug concentrations or are unrelated to protein binding dynamics. High protein intake, for instance, is more likely to increase protein levels within the blood, potentially leading to a decrease in free drug concentration instead. Low lipid solubility would generally affect the drug's ability to cross cell membranes rather than its free concentration in circulation. Lastly, an excess of albumin in the bloodstream would likely bind more drug molecules, alternatively reducing free drug concentration.