Taxaceae and Cephalotaxaceae

Taxaceae and Cephalotaxaceae

Biodiversity, Chemodiversity, and Pharmacotherapy
2021, Pages 123-189
Taxaceae and Cephalotaxaceae

Chapter 4 - Drug metabolism and pharmacokinetic diversity of Taxus medicinal compounds

https://doi.org/10.1016/B978-0-12-823975-9.00004-3Get rights and content

Abstract

Drug metabolism and pharmacokinetic (DMPK) studies of Taxaceae/Cephalotaxaceae natural products, their semisynthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion, and toxicity (ADME/T) profiles. Natural and semisynthetic taxanes may cause and could be affected by drug–drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date, these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug-metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single-nucleotide polymorphisms are being revealed. Herein the latest knowledge on these topics as well as the gaps in knowledge of the DMPK issues of Taxaceae/Cephalotaxaceae compounds are summarized. DDIs significantly impact the pharmacokinetics/pharmacodynamics performance of taxanes and coadministered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxaceae/Cephalotaxaceae compounds, species, and Taxaceae/Cephalotaxaceae-involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial to the translation of bench findings to the clinical applications.

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