New Approach to Reduce the Overhigh Plasma Concentration of Captopril by the Formation of Zinc Coordination Polymer

Captopril
is an antihypertension drug, it has side effects of vertigo,
headache, and functional gastrointestinal disorders due to its overhigh
plasma concentration. In addition, captopril undergoes oxidation at
its thiol to yield captopril disulfide. In order to reduce its release
rate and increase its oxidation stability, coordination polymer of
captopril with zinc ion was prepared and its structure was determined
by single crystal X-ray diffraction. The results of solubility measurements
indicate that the apparent solubility and intrinsic dissolution rate
of captopril can be dramatically decreased after the formation of
coordination polymer. Pharmacokinetic studies in rats reveal that
the plasma concentration of captopril can be reduced by the formation
of zinc coordination polymer, with maximum plasma concentration reduced
from 2.53 μg/mL for captopril to 0.99 μg/mL for the zinc
coordination polymer. Moreover, the oxidation stability of captopril
is simultaneously improved by the formation of zinc coordination polymer.