<prompt> All of the following factors tend to increase the volume of distrubtion of a drug exceptHigh plasma protein bindingLow ionization at physiological pH valuesHigh lipid solubilityHigh tissue binding  <response>: Ref-katzung 10e per,35 If a drug is highly bound to plasma proteins ,it is more likely to stay in blood.thus its Vd will be less . Low ionization ours the distribution of a drug because unionized molecules can cross the membrane of blood vessels and the tissue More lipid soluble drugs can easily cross the membrane and are more likely to be highly distributed 