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Data from: Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake in vivo

Drabison, Thomas1; Ahmed, Eman1; Colasanti, Nathan1; Weber, Robert1; Sparreboom, Alex1; Eisenmann, Eric1

Published Apr 16, 2026 on Dryad. https://doi.org/10.5061/dryad.f1vhhmh9d

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Abstract

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. 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 influence the pharmacokinetics or pharmacodynamics of the OATP1B substrates CDCA-24G or paclitaxel. Furthermore, Oatp1b deficiency did not alter the pharmacokinetics of ribociclib. Our findings suggest that clinically significant OATP1B-mediated interactions are not anticipated with CDK4/6 inhibitors, either as victims or perpetrators, which supports ongoing clinical trials investigating the co-administration of CDK4/6 inhibitors with OATP1B substrates and inhibitors.