Alpha-1-acid glycoprotein (AAGP) binds primarily which type of drugs?

• A. Basic cationic drugs
• B. Weak acids
• C. Neutral compounds
• D. Large hydrophobic molecules

Answer: (A)

Basic cationic drugs are the type that alpha-1-acid glycoprotein preferentially binds. Alpha-1-acid glycoprotein carries negative charges at physiological pH thanks to its sialic acid residues, so it binds positively charged (basic) drugs through ionic interactions. This causes these drugs to exist more in the bound form in plasma, reducing the freely circulating portion that can exert effect or be cleared quickly. In contrast, acidic drugs tend to bind mainly to albumin, and many neutral or very large hydrophobic drugs bind differently, often with less dependence on AAG. Examples of basic drugs that commonly bind AAG include propranolol and lidocaine.