Interspecies differences in stability kinetics and plasma esterases involved in hydrolytic activation of curcumin diethyl disuccinate, a prodrug of curcumin.

ABSTRACT: The investigation of in vitro plasma metabolism of ester prodrugs is an important part of in vitro ADME assays during preclinical drug development. Here, we show that the in vitro metabolism including plasma stability and metabolizing enzymes of curcumin diethyl disuccinate (CDD), an ester prodrug of curcumin, in dog and human plasma are similar but markedly different from those in rat plasma. HPLC and nonlinear regression analyses indicated that the hydrolysis of CDD in plasma followed a consecutive pseudo-first order reaction. The rapid hydrolytic cleavage of CDD in rat, dog, and human plasma was accelerated by plasma esterases in the following order: rat ≫ human > dog. LC-Q-TOF/MS analysis showed that the cleavage of ester bonds of CDD is preferential at the phenoli

SUBMITTER: Ratnatilaka Na Bhuket P 

PROVIDER: S-EPMC9060607 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature