Publications by authors named "Yuta Tamemoto"
Herein, we aimed to determine the significance of drug interactions (DIs) between ritonavir and direct oral anticoagulants (DOACs) and identify the involved cytochrome P450 (CYP) isoenzymes. Using an in vitro cocktail method with human liver microsomes (HLM), we observed that ritonavir strongly inhibited CYPs in the following order: CYP3A, CYP2C8, CYP2D6, CYP2C9, CYP2C19, CYP2B6, and CYP2J2 (IC: 0.023-6.
View Article and Find Full Text PDFArticle Synopsis
- The study developed a new mechanistic static pharmacokinetic (MSPK) framework to better predict drug interactions, addressing limitations of existing models that can't use in vitro data or differentiate CYP enzyme contributions.
- By analyzing drug interactions involving multiple CYP isoenzymes and using both in vivo and in vitro data, the researchers could estimate changes in drug concentration and elimination for a wide range of drug combinations.
- The framework proved to be effective in managing drug interactions, illustrating its potential to enhance our understanding of how different drugs might affect each other in the body.
Drug absorption from the gastrointestinal tract is often restricted by efflux transport by P-glycoprotein (P-gp) and metabolism by CYP3A4. Both localize in the epithelial cells, and thus, their activities are directly affected by the intracellular drug concentration, which should be regulated by the ratio of permeability between apical (A) and basal (B) membranes. In this study, using Caco-2 cells with forced expression of CYP3A4, we assessed the transcellular permeation of A-to-B and B-to-A directions and the efflux from the preloaded cells to both sides of 12 representative P-gp or CYP3A4 substrate drugs and obtained the parameters for permeabilities, transport, metabolism, and unbound fraction in the enterocytes (f) using simultaneous and dynamic model analysis.
View Article and Find Full Text PDFArticle Synopsis
- A study evaluated how eight cytochrome P450 (CYP) isoenzymes inhibit various substances, including pesticides, to assess the risks of drug interactions (DIs), especially with CYPs.
- Voriconazole, an azole antifungal, was found to significantly inhibit CYP2B6, affecting cyclophosphamide's metabolism and reducing its adverse effects in mice by about 50%.
- Analysis of adverse event databases revealed that combining cyclophosphamide and azoles like voriconazole mostly led to reduced instances of neutropenia, hemorrhagic cystitis, and alopecia, suggesting that CYP2B6-mediated drug interactions need closer examination in clinical practice.