title: Volume of Distribution in Drug Design.
abstract: Volume of distribution is one of the most important pharmacokinetic properties of a drug candidate. It is a major determinant of half-life and dosing frequency of a drug. For a similar log P, a basic molecule will tend to exhibit higher volume of distribution than a neutral molecule. Acids often exhibit low volumes of distribution. Although a design strategy against volume of distribution can be advantageous in achieving desirable dosing regimen, it must be well-directed in order to avoid detrimental effects to other important properties. Strategies to increase volume of distribution include adding lipophilicity and introducing basic functional groups in a way that does not increase metabolic clearance.
authors: †4 The Maltings, Walmer, Kent CT14 7AR, U.K.
authors: Dennis A
authors: DA
authors: Smith
authors: ‡Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Cambridge, Massachusetts 02139, United States.
authors: Kevin
authors: K
authors: Beaumont
authors: ‡Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Cambridge, Massachusetts 02139, United States.
authors: Tristan S
authors: TS
authors: Maurer
authors: §Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Groton, Connecticut 06340, United States.
authors: Li
authors: L
authors: Di
mesh_terms: D015195:Drug Design; D006207:Half-Life; D010599:Pharmacokinetics