Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake <em>in vivo</em>

Ribociclib is a CDK4/6 inhibitor used to treat HR+/HER2- breast cancer. Despite regulatory documents suggesting that ribociclib may inhibit both CYP3A and OATP1B-type transport in vitro, it is unclear whether CDK4/6 inhibitors interact with these mechanisms in vivo. Based on two cases of severe rhabdomyolysis in patients taking a CDK4/6 inhibitor and simvastatin, a CYP3A and OATP1B substrate, we tested the hypothesis that CDK4/6 inhibitors may precipitate drug-drug interactions through these mechanisms. We assessed the ability of CDK4/6 inhibitors to inhibit CYP3A and OATP1B-type transporters. Based on these data, we performed pharmacokinetic studies and toxicity assessments to determine whether ribociclib is a substrate or inhibitor of OATP1B-type transport in vivo.&nbsp;Ribociclib inhibited the metabolism of triazolam, a CYP3A probe, in vivo. Additionally, CDK4/6 inhibitors inhibited OATP1B-type transporters in vitro. However, ribociclib, the most potent OATP1B inhibitor, did not infl..., , # Data from: Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake *in vivo* Dataset DOI: [10.5061/dryad.f1vhhmh9d](https://doi.org/10.5061/dryad.f1vhhmh9d) ## Description of the data and file structure This database includes data from efforts to characterize the relationship between CDK4/6 inhibitors, especially ribociclib, and OATP1B-type transporters. These data include values from: cellular uptake experiments with fluorescent and radioactive substrates; murine pharmacokinetic studies completed with triazolam, ribociclib, paclitaxel, or pravastatin; and behavioral assays. ### Files and variables #### File: Fig_1.xlsx **Description:** Pharmacokinetic study using triazolam as a probe for CYP3A activity. The study objective is to determine the inhibition of CYP3A-mediated metabolism by ribociclib. ##### Independent Variables * Time (min), treatment (ribociclib versus vehicle) ##### Dependent Variables * Triazolam/OH-triazolam ratio #### File: Fig_2.xlsx **De..., ,