(Apparent)volume of distribution Some drugs have a Vd that is much larger than total body water.A large Vd may indicate that the drug is concentrated intracellularly,with a resulting low concentration in the plasma.Many weak bases, such as the antidepressant fluoxetine(Prozac),have a large Vd(40-55 L)because of the phenomenon of intracellular ion trapping.Weak bases are less ionized within plasma than they are within cells because intracellular fluid usually has a lower pH than extracellular fluid.After a weak base diffuses into a cell,a larger fraction is ionized in the more acidic intracellular fluid.This restricts its diffusion out of a cell and results in a large Vd.• Some drugs have a Vd that is much larger than total body water. A large Vd may indicate that the drug is concentrated intracellularly, with a resulting low concentration in the plasma. Many weak bases, such as the antidepressant fluoxetine (Prozac), have a large Vd (40‐55 L) because of the phenomenon of intracellular ion trapping. Weak bases are less ionized within plasma than they are within cells because intracellular fluid usually has a lower pH than extracellular fluid. After a weak base diffuses into a cell, a larger fraction is ionized in the more acidic intracellular fluid. This restricts its diffusion out of a cell and results in a large Vd. (Apparent) volume of distribution