Journal ArticleDOI
Esterase Activities in the Blood, Liver and Intestine of Several Preclinical Species and Humans
TLDR
Substantial species differences in activity of these esterases were observed between the mouse, rat, dog monkey and human, and such species differences must be considered when using these preclinical species to optimize the pharmacokinetic properties of ester compounds intended for human use.Abstract:
Species and tissue differences in the activity of three major classes of esterases, carboxylesterase (CE), butyrylcholinesterase (BChE) and paraoxonase (PON), were studied. Substantial species differences in activity of these esterases were observed between the mouse, rat, dog monkey and human. Such species differences must be considered when using these preclinical species to optimize the pharmacokinetic properties of ester compounds intended for human use.read more
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Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
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Contributions of Intestine and Plasma to the Presystemic Bioconversion of Vicagrel, an Acetate of Clopidogrel
Zhixia Qiu,Ning Li,Ling Song,Yang Lu,Jing Jing,Harendra S. Parekha,Wenchao Gao,Fengjie Tian,Xin Wang,Shuangxia Ren,Xijing Chen +10 more
TL;DR: The findings rationalized the prodrug design hypothesis that vicagrel could overcome the extensive invalid hydrolysis of clopidogrel by the hepatic CE1 but experience the extensive hydrolytic to 2-oxo-clopidodogrel and subsequent oxidation to AM in the intestine and supported the theory of improved pharmacological activity through facilitated formation of 2-Oxo-Clopidol.
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Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans.
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TL;DR: Comparing the predicted and observed human PK from the phase I study, the dose‐normalized concentration‐time profiles ofαCD70_MED‐A and the total αCD70 were largely within the 5th‐95th percentile of the predicted profiles.