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31 results on '"Schmidt, Keith T."'

2. Pharmacokinetics and pharmacogenomics of ribociclib in black patients with metastatic breast cancer the LEANORA study

Author

Schlam, Ilana, Smith, D. Max, Peer, Cody, Sissung, Tristan, Schmidt, Keith T., Tan, Ming, Chitalia, Ami, Bishopric, Nanette H., Steinberg, Seth, Choo-Wosoba, Hyoyoung, Napoli, Giulia, Gallagher, Christopher, Ashai, Nadia, Whitaker, Kristen, Mainor, Candace, Tiwari, Shruti, Swanson, Nicole, Malloy, Stacy, Isaacs, Claudine, Figg, William Douglas, and Swain, Sandra M.

Published
2024
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10. A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug–Drug Interaction Liabilities

Author

Li, Yang, primary, Jin, Yan, additional, Taheri, Hanieh, additional, Schmidt, Keith T., additional, Gibson, Alice A., additional, Buck, Stefan A. J., additional, Eisenmann, Eric D., additional, Mathijssen, Ron H. J., additional, Figg, William D., additional, Baker, Sharyn D., additional, Sparreboom, Alex, additional, and Hu, Shuiying, additional

Published
2022
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11. A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide

Author

Schmidt, Keith T, primary, Karzai, Fatima, additional, Bilusic, Marijo, additional, Cordes, Lisa M, additional, Chau, Cindy H, additional, Peer, Cody J, additional, Wroblewski, Susan, additional, Huitema, Alwin D R, additional, Schellens, Jan H M, additional, Gulley, James L, additional, Dahut, William L, additional, Figg, William D, additional, and Madan, Ravi A, additional

Published
2022
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12. A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide

Author

Apotheek O&O&O, Cancer, Schmidt, Keith T., Karzai, Fatima, Bilusic, Marijo, Cordes, Lisa M., Chau, Cindy H., Peer, Cody J., Wroblewski, Susan, Huitema, Alwin D.R., Schellens, Jan H.M., Gulley, James L., Dahut, William L., Figg, William D., Madan, Ravi A., Apotheek O&O&O, Cancer, Schmidt, Keith T., Karzai, Fatima, Bilusic, Marijo, Cordes, Lisa M., Chau, Cindy H., Peer, Cody J., Wroblewski, Susan, Huitema, Alwin D.R., Schellens, Jan H.M., Gulley, James L., Dahut, William L., Figg, William D., and Madan, Ravi A.

Published
2022

13. A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities

Author

Li, Yang, Jin, Yan, Taheri, Hanieh, Schmidt, Keith T., Gibson, Alice A., Buck, Stefan A. J., Eisenmann, Eric D., Mathijssen, Ron H. J., Figg, William D., Baker, Sharyn D., Sparreboom, Alex, Hu, Shuiying, Li, Yang, Jin, Yan, Taheri, Hanieh, Schmidt, Keith T., Gibson, Alice A., Buck, Stefan A. J., Eisenmann, Eric D., Mathijssen, Ron H. J., Figg, William D., Baker, Sharyn D., Sparreboom, Alex, and Hu, Shuiying

Abstract

In recent years, various endogenous compounds have been proposed as putative biomarkers for the hepatic uptake transporters OATP1B1 and OATP1B3 that have the potential to predict transporter-mediated drug-drug interactions (DDIs). However, these compounds have often been identified from top-down strategies and have not been fully utilized as a substitute for traditional DDI studies. In an attempt to eliminate observer bias in biomarker selection, we applied a bottom-up, untargeted metabolomics screening approach in mice and found that plasma levels of the conjugated bile acid chenodeoxycholate-24-glucuronide (CDCA-24G) are particularly sensitive to deletion of the orthologous murine transporter Oatp1b2 (31-fold increase vs. wild type) or the entire Oatp1a/1b(-/-)cluster (83-fold increased), whereas the humanized transgenic overexpression of hepatic OATP1B1 or OATP1B3 resulted in the partial restoration of transport function. Validation studies with the OATP1B1/OATP1B3 inhibitors rifampin and paclitaxel in vitro as well as in mice and human subjects confirmed that CDCA-24G is a sensitive and rapid response biomarker to dose-dependent transporter inhibition. Collectively, our study confirmed the ability of CDCA-24G to serve as a sensitive and selective endogenous biomarker of OATP1B-type transport function and suggests a template for the future development of biomarkers for other clinically important xenobiotic transporters.

Published
2022

18. Whole-exome sequencing reveals germline-mutated small cell lung cancer subtype with favorable response to DNA repair–targeted therapies

Author

Tlemsani, Camille, primary, Takahashi, Nobuyuki, additional, Pongor, Lorinc, additional, Rajapakse, Vinodh N., additional, Tyagi, Manoj, additional, Wen, Xinyu, additional, Fasaye, Grace-Ann, additional, Schmidt, Keith T., additional, Desai, Parth, additional, Kim, Chul, additional, Rajan, Arun, additional, Swift, Shannon, additional, Sciuto, Linda, additional, Vilimas, Rasa, additional, Webb, Santhana, additional, Nichols, Samantha, additional, Figg, William Douglas, additional, Pommier, Yves, additional, Calzone, Kathleen, additional, Steinberg, Seth M., additional, Wei, Jun S., additional, Guha, Udayan, additional, Turner, Clesson E., additional, Khan, Javed, additional, and Thomas, Anish, additional

Published
2021
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19. Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors

Author

Schmidt, Keith T., primary, Huitema, Alwin D. R., additional, Dorlo, Thomas P. C., additional, Peer, Cody J., additional, Cordes, Lisa M., additional, Sciuto, Linda, additional, Wroblewski, Susan, additional, Pommier, Yves, additional, Madan, Ravi A., additional, Thomas, Anish, additional, and Figg, William D., additional

Published
2020
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22. Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors.

Author

Schmidt, Keith T, Huitema, Alwin D R, Dorlo, Thomas P C, Peer, Cody J, Cordes, Lisa M, Sciuto, Linda, Wroblewski, Susan, Pommier, Yves, Madan, Ravi A, Thomas, Anish, Figg, William D, Schmidt, Keith T, Huitema, Alwin D R, Dorlo, Thomas P C, Peer, Cody J, Cordes, Lisa M, Sciuto, Linda, Wroblewski, Susan, Pommier, Yves, Madan, Ravi A, Thomas, Anish, and Figg, William D

Abstract

PURPOSE: NLG207 (formerly CRLX101) is a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor, camptothecin (CPT). The present study sought to characterize the complex pharmacokinetics (PK) of NLG207 and better describe CPT release from nanoparticles using a population PK (popPK) model. METHODS: From 27 patients enrolled on two phase II clinical trials (NCT02769962 and NCT03531827), dense sampling was performed up to 48 h post-administration of NLG207 during cycle one and six of treatment; samples were also collected at ~ 360 h post-dose. Conjugated and free CPT concentrations were quantified from each sample, resulting in 477 observations to build a popPK model using non-linear mixed-effects modeling. RESULTS: The PK of NLG207 was characterized by combining two linear two-compartment models with first-order kinetics each to describe nanoparticle-bound (conjugated) and free CPT. Allometric scaling based on body weight provided the best body-size descriptor for all PK parameters. The typical volumes of distribution of the conjugated CPT central and free CPT central compartments were 3.16 L (BSV CV%; 18.1%) and 21.1 L (CV%; 79.8%), respectively. CPT release from the nanoparticle formulation was characterized via an initial rapid clearance of 5.71 L/h (CV%; 62.6%), which decreased via first-order decay (estimated half-life of 0.307 h) to the steady-state value of 0.0988 L/h (CV%; 33.5%) by ~ 4 h after end of infusion. Renal clearance of free CPT was 0.874 L/h (CV%; 42.2%). CONCLUSION: The popPK model confirmed nanoparticle behavior of conjugated CPT and mechanistically characterized CPT release from NLG207. The current analysis provides a strong foundation for future study as a potential predictive tool in ongoing NLG207 clinical trials.

Published
2020
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23. Population pharmacokinetic analysis of nanoparticle-bound and free camptothecin after administration of NLG207 in adults with advanced solid tumors

Author

Cancer, Apotheek Onderzoek, Schmidt, Keith T., Huitema, Alwin D.R., Dorlo, Thomas P.C., Peer, Cody J., Cordes, Lisa M., Sciuto, Linda, Wroblewski, Susan, Pommier, Yves, Madan, Ravi A., Thomas, Anish, Figg, William D., Cancer, Apotheek Onderzoek, Schmidt, Keith T., Huitema, Alwin D.R., Dorlo, Thomas P.C., Peer, Cody J., Cordes, Lisa M., Sciuto, Linda, Wroblewski, Susan, Pommier, Yves, Madan, Ravi A., Thomas, Anish, and Figg, William D.

Published
2020

31. Combination treatment in metastatic castration-resistant prostate cancer: can we safely boost efficacy by adding radium-223?

Author

Knechel, Martina A., Schmidt, Keith T., and Figg, William D.

Subjects
*CASTRATION-resistant prostate cancer, *ABIRATERONE acetate, *RANDOMIZED controlled trials, *TREATMENT effectiveness
Abstract

ERA 223, a phase III, international, multicenter, double-blind study published in Lancet Oncology, was the first randomized controlled trial to investigate combined radium-223 (Ra-223) and abiraterone acetate plus prednisone or prednisolone (AAP) therapy. The data from ERA 223 demonstrated no increase in efficacy for this combination over AAP alone, and instead identified a significant safety concern due to the higher risk of fracture in the co-treatment group. The surprising results of this trial likely stem from the compounding osteoporotic effects of the different treatments, particularly the addition of prednisone, and supplementing therapy regimens with osteoprotective agents may aid in mitigating this safety risk. [ABSTRACT FROM AUTHOR]

Published
2020
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