Abstract

Volume of distribution (Vd) is an important pharmacokinetic parameter. While conceptually un physiological, Vd remains a practical indicator for the accessibility of a drug to the tissues as well as a key determinant for the exposure profile. This is particularly true for both central nervous system and oncologic therapeutics because the biological targets are often resided in peripheral body tissues. For instance, antidepressant selective serotonin reuptake inhibitors and anticancer poly (ADP-ribose) polymerase inhibitors like much effective therapeutics, exhibit desirable pharmacokinetic properties, large Vd in particular that is consistent with their intended therapeutic applications.

Physiochemical properties of small-molecule drugs directly impact their disposition in the body, namely absorption, distribution, metabolism, and elimination. Lipophilicity, gauging upon ClogP, and basicity have been shown to be positively associated with Vd, due in part to the roles they play in cell permeation and tissue binding, respectively.

To ensure therapeutic successes in complex drug development, a plethora of aspects and requirements, besides mechanism of action, need to be well comprehended and fulfilled. We believe that Vd would be among them, especially if the therapeutic moieties are intended to target the tissues of the central nervous system and solid tumors.