Drug metabolism and disposition diversity of Ranunculales phytometabolites: a systems perspective

Although investigations in metabolism and pharmacokinetics of Ranunculales phytometabolites are booming, data obtained from human and animal studies have not been summarized as a whole to outline current trends and to predict future development.

Here, we highlight the current knowledge, as well as the challenges around the DMPK (drug metabolism and pharmacokinetics) associated concerns in streamlining drug research and therapeutic use of Ranunculales phytometabolites. Data from various in vivo and in vitro models are classified and discussed. DMPK characteristics of Ranunculales phytometabolites are summarized and presented according to the phylogenetic relationship of families and genera. This review also presents an overview of the complex interaction between drug metabolizing enzymes/transporters and phytochemicals, as well as of the most advanced approaches in the relevant field.

Since species-specific differences in DMPK exist, data obtained from animal studies may not be sufficient to predict drug metabolism reactions in humans. Omics-based methodologies (genomics, epigenomics, transcriptomics, proteomics, microbiomics, and metabolomics) should be used to enhance the reliability of DMPK prediction. The fluorescent probes may bridge the gap between conventional models and in vivo clinical studies in humans and provide a consistent basis for DMPK assay development.