Comparison of enzymatic hydrolysis of pilocarpine prodrugs in human plasma, rabbit cornea, and butyrylcholinesterase solutions.

Various bispilocarpic acid diesters (double prodrugs of pilocarpine) were synthesized, and their in vitro esterase catalyzed hydrolysis was evaluated in diluted human plasma, rabbit cornea homogenate, and specific butyrylcholinesterase solution. The structural changes greatly affected the rate of enzymatic hydrolysis of the prodrugs. Bispilocarpic acid with 2 cyclopropane substituents was the most stable derivative, whereas bispilocarpic acid with 2 cyclobutane substituents was the most labile derivative.