COMPARISON OF ENZYMATIC-HYDROLYSIS OF PILOCARPINE PRODRUGS IN HUMAN PLASMA, RABBIT CORNEA, AND BUTYRYLCHOLINESTERASE SOLUTIONS

Various bispilocarpic acid diesters (double prodrugs of pilocarpine) w ere synthesized, and their in vitro esterase catalyzed hydrolysis was evaluated in diluted human plasma, rabbit cornea homogenate, and speci fic butyrylcholinesterase solution. The structural changes greatly aff ected 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 mos t labile derivative. The charged bispilocarpic acid diester hydrolyzed more slowly than the uncharged form. Comparison of the results obtain ed from different plasma and cornea homogenate batches is difficult be cause of the variety of the enzyme systems involved. This variety also makes comparing the results between different laboratories difficult.