The lower the pH of a solution the (more/less) lipid soluble it becomes.

The lower the pH of a solution the (more/less) lipid soluble it becomes.

• A. More
• B. Less
• C. The Same
• D. Depends on the drug

Answer: (B)

Lipid solubility tracks with the drug’s ionization state. Non-ionized (uncharged) forms dissolve in and cross lipid membranes readily, while ionized forms do not. For a weak base, lowering the pH shifts the equilibrium toward the protonated, charged form (BH+). That protonated form is less lipid soluble, so as pH decreases, the drug becomes less lipid soluble. This is why, for many anesthetic drugs that are weak bases, a more acidic environment reduces their lipid solubility. (Note: for weak acids, lowering pH increases the non-ionized, lipid-soluble form, so the reverse would be true.)

Lipid solubility tracks with the drug’s ionization state. Non-ionized (uncharged) forms dissolve in and cross lipid membranes readily, while ionized forms do not. For a weak base, lowering the pH shifts the equilibrium toward the protonated, charged form (BH+). That protonated form is less lipid soluble, so as pH decreases, the drug becomes less lipid soluble. This is why, for many anesthetic drugs that are weak bases, a more acidic environment reduces their lipid solubility. (Note: for weak acids, lowering pH increases the non-ionized, lipid-soluble form, so the reverse would be true.)