1. Pilocarpine Indication: glaucoma
Doses: 0.5 – 4% eye drops; 2-6 times daily
Side-effects: intense miosis, cycloplegia
PROBLEMS:
short duration of action
adverse effects
low compliance
low bioavailability (1%)
logP is about 0
weak base
Can we make pilocarpine that avoids these problems

3. Prodrugs covalent modification of parent drug parent drug + pro-moiety
pro-moiety cleaves based on enzymatic reaction
properties of parent drug can be improved
ADME
solubility
safety

4. Pilocarpine prodrugs - expected scheme in the eye
Bispilocarpic acid diesters
Bispilocarpic acid monoesters
Pilocarpine
Goal is to make eyedrop solution
Long duration of action ( 1x daily administration)
Reduced peak concentration of pilocarpine
 side-effects reduced