You are attempting to modify an existing antimicrobial drug to treat intestinal bacterial infections. The drug has numerous unwanted side effects when it reaches the bloodstream, so you want to enhance the availability of the drug in the GI tract, but limit its appearance in the bloodstream. Which of the following would have the desired effect? Select all that apply.
A. Design the drug so its metabolism in the liver is reduced
B. Reduce the binding of the drug to serum albumin
C. Increase the molecular weight of the drug
D. Modify the drug so it is charged/more polar at pH <3.0
E. Modify the drug so it is uncharged at pH <3.0