Drug–tea polyphenol interaction

Abstract

Propericiazine (PCZ) is an antipsychotic agent used for the treatment and the prevention of relapse of schizophrenia. We found that when an oral solution containing PCZ was mixed with a green tea drink, the residual content of PCZ was reduced by forming an insoluble complex between PCZ and tea polyphenol. In this study, the mechanism underlying the incompatibility of PCZ with green tea polyphenol (GTP) in the solution was clarified by isothermal titration microcalorimetry (ITC). Both solutions of 27.4 mM PCZ and 2.2 mM (−)-epigallocatechin gallate (EGCg), which is a main ingredient of GTP, were mixed and then PCZ in the filtrate was reduced to approximately 60 %. According to measurement at 298 K by ITC, PCZ formed an insoluble complex with EGCg at an associate constant (K) of 4.75 × 102 M−1 exothermically, ΔH = −40.0 kJ mol−1. When (−)-epicatechin gallate (ECg) was used as the GTP, PCZ interacted with ECg with K and ΔH values of 3.74 × 102 M−1 and −22.1 kJ mol−1, respectively. On the other hand, little heat of the reaction between PCZ and (−)-epigallocatechin or (−)-epicatechin was observed. The results indicated that the main reason for this incompatibility was the formation of an insoluble complex by PCZ and a gallate-type GTP such as EGCg and ECg in the aqueous solution.