Species-specific in vivo exposure assessment and in vivo-in vitro correlation of the carboxylate esters prodrug HD56 targeting FK506 binding proteins: The pivotal role of humanized mice.

HD561, which was designed to enhance nerve growth, was re-engineered into HD56, a carboxylic acid ester prodrug. The goal of this study was to compare the druggability, species differences, and the correlation between in vitro and in vivo transformation of HD56 to HD561 from a pharmacokinetic (PK) perspective, offering a scientific basis for HD56's clinical research. The bidirectional transmembrane transport of HD56 and HD561 was investigated using Caco-2 cells and LLC-PK1 cells overexpressing MDR1 monolayer cells.

Simultaneous determination of HD56, a novel prodrug, and its active metabolite in cynomolgus monkey plasma using LC-MS/MS for elucidating its pharmacokinetic profile.

An LC-MS/MS method was developed and validated for the simultaneous determination of the carboxylic acid ester precursor HD56 and the active product HD561 in cynomolgus monkey plasma. Then, the pharmacokinetic characteristics of both compounds following single and multiple i.g.