Papers

InsightRX-led papers

van Os W, O’Jeanson A, Troisi C, Liu C, Brooks JT, Hughes JH, Tong DMH, Keizer RJ. (2025). Machine Learning-Based Model Selection and Averaging Outperform Single-Model Approaches for a Priori Vancomycin Precision Dosing. CPT Pharmacometrics Syst Pharmacol Jul 30. https://doi.org/10.1002/psp4.70084

Tong DMH, Hughes M-SA, Hu J, Pearson JC, Kubiak DW, Dionne BW, Hughes JH. (2025). Comparing two-sample log-linear exposure estimation with Bayesian model-informed precision dosing of tobramycin in adult patients with cystic fibrosis. Antimicrob Agents Chemother. 69(2):e0104024. https://doi.org/10.1128/aac.01040-24

Hughes MA, Hughes JH, Endicott J, Langton M, Ahern JW, Keizer RJ. (2024) Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity. Ther Drug Monit. 46(5):575-583. https://doi.org/10.1097/FTD.0000000000001214

Hughes JH, Long-Boyle J, Keizer RJ. (2024) Maximum a posteriori Bayesian methods out-perform non-compartmental analysis for busulfan precision dosing. J Pharmacokinet Pharmacodyn. 51(3):279-288. https://doi.org/10.1007/s10928-024-09915-w

Hughes, J. H., Tong, D. M. H., Burns, V., Daly, B., Razavi, P., Boelens, J. J., Goswami, S., & Keizer, R. J. (2023). Clinical decision support for chemotherapy-induced neutropenia using a hybrid pharmacodynamic/machine learning model. CPT: Pharmacometrics & Systems Pharmacology. https://doi.org/10.1002/psp4.13019.

Hughes, J. H., Woo, K. H., Keizer, R. J. & Goswami, S. (2022). Clinical decision support for precision dosing: opportunities for enhanced equity and inclusion in healthcare. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.2799

Hughes, J. H., Tong, D. M. H., Faldasz, J. D., Frymoyer, A., Keizer, R. J. (2022). Evaluation of Neonatal and Paediatric Vancomycin Pharmacokinetic Models and the Impact of Maturation and Serum Creatinine Covariates in a Large Multicentre Data Set. Clin Pharmacokinet. https://doi.org/10.1007/s40262-022-01185-4

Tong, D. M. H., Hughes, J. H., Keizer, R. J. (2022) Evaluating and Improving Neonatal Gentamicin Pharmacokinetic Models Using Aggregated Routine Clinical Care Data. Pharmaceutics. 14(10):2089. https://doi.org/10.3390/pharmaceutics14102089.

Hughes, J. H., & Keizer, R. J. (2021). A hybrid machine learning/pharmacokinetic approach outperforms maximum a posteriori Bayesian estimation by selectively flattening model priors. CPT: Pharmacometrics & Systems Pharmacology, 10(10), 1150–1160. https://doi.org/10.1002/psp4.12684

Tong, D. M. H., Hughes, J. H., & Keizer, R. J. (2021). Use of Age-Adjusted Serum Creatinine in a Vancomycin Pharmacokinetic Model Decreases Predictive Performance in Elderly Patients. Therapeutic Drug Monitoring, 43(1), 139–140. https://doi.org/10.1097/FTD.0000000000000819

Hughes, J. H., Tong, D. M. H., Lucas, S. S., Faldasz, J. D., Goswami, S., & Keizer, R. J. (2021). Continuous Learning in Model‐Informed Precision Dosing: A Case Study in Pediatric Dosing of Vancomycin. Clinical Pharmacology & Therapeutics, 109(1), 233–242. https://doi.org/10.1002/cpt.2088

Keizer, R. J., Dvergsten, E., Kolacevski, A., Black, A., Karovic, S., Goswami, S., & Maitland, M. L. (2020). Get Real: Integration of Real-World Data to Improve Patient Care. Clinical Pharmacology and Therapeutics, 107(4), 722–725. https://doi.org/10.1002/cpt.1784

Keizer, R. J., ter Heine, R., Frymoyer, A., Lesko, L. J., Mangat, R., & Goswami, S. (2018). Model-Informed Precision Dosing at the Bedside: Scientific Challenges and Opportunities. CPT: Pharmacometrics & Systems Pharmacology, 7(12), 785–787. https://doi.org/10.1002/psp4.12353

External collaborations

Weersink RA, Keizer RJ, Derijks LJJ. (2025). Simulated Dosing Regimens of Subcutaneous Infliximab in Adults and Children with Inflammatory Bowel Disease: Exploring Switch and Initiation Strategies. Eur J Drug Metab Pharmacokinet 50(5):419-430. https://doi.org/10.1007/s13318-025-00959-y

Bayoumy AB, de Boer NKH, Keizer RJ, Derijks LJJ. (2025) Population Pharmacokinetics Model of Thioguanine in Patients with Inflammatory Bowel Disease. Clin Pharmacokinet. 64(8):1255-1262. https://doi.org/10.1007/s40262-025-01532-1

Dvorak CC, Cho S, Salinas Cisneros G, Higham CS, Chu J, Winestone LE, Temple WC, Kharbanda S, Shimano KA, Avagyan S, Pauerstein PT, Huang JN, Cheng G, Lalefar N, Aguayo-Hiraldo P, Keizer RJ, Pulsipher MA, Long-Boyle JR. (2025) High Melphalan Exposure Increases the Risk of Graft-Versus-Host Disease in Pediatric Patients Undergoing Alpha-Beta T-Cell Depleted Haploidentical Transplantation. Transplant Cell Ther. 31(6):384.e1-384.e15. https://doi.org/10.1016/j.jtct.2025.03.020

Lu J, Choi K, Eremeev M, Gobburu J, Goswami S, Liu Q, Mo G, Musante CJ, Shahin MH. Large Language Models and Their Applications in Drug Discovery and Development: A Primer. (2025). Clin Transl Sci. 18(4):e70205. https://doi.org/10.1111/cts.70205

Bourgonje AR, Dubinsky MC, Keizer RJ, Dreesen E, Mian P. (2025). Model-informed precision dosing in inflammatory bowel diseases. Trends Pharmacol Sci. 46(1):9-19. https://doi.org/10.1016/j.tips.2024.11.003

Shahin MH, Goswami S, Lobentanzer S, Corrigan BW. Agents for Change: Artificial Intelligent Workflows for Quantitative Clinical Pharmacology and Translational Sciences. (2025) Clin Transl Sci. 18(3):e70188. https://doi.org/10.1007/10.1111/cts.70188

Heida A, Jager NGL, Aarnoutse RE, de Winter BCM, de Jong H, Keizer RJ, Cornelissen EAM, Ter Heine R. (2024) Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients. Eur J Clin Pharmacol. 80(11):1761-1771. https://doi.org/10.1007/s00228-024-03743-0

Alsoud D, Moes DJAR, Wang Z, Soenen R, Layegh Z, Barclay M, Mizuno T, Minichmayr IK, Keizer RJ, Wicha SG, Wolbink G, Lambert J, Vermeire S, de Vries A, Papamichael K, Padullés-Zamora N, Dreesen E. (2024) Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 46(3):291-308. https://doi.org/10.1097/FTD.0000000000001204

Jansen AME, Snijdelaar K, Keizer RJ, Spriet I, Dreesen E, Brüggemann RJM, Ter Heine R. (2024) Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole. Clin Pharmacokinet. 63(5):645-656. https://doi.org/10.1007/s40262-024-01361-8

Bevers NC, Keizer RJ, Wong DR, Aliu A, Pierik MJ, Derijks LJJ, van Rheenen PF. (2024) Performance of Eight Infliximab Population Pharmacokinetic Models in a Cohort of Dutch Children with Inflammatory Bowel Disease. Clin Pharmacokinet. 63(4):529-538. https://doi.org/10.1007/s40262-024-01354-7

de Klaver, P. A. G., Keizer, R. J., Ter Heine, R., Smits, L., Boekema, P. J., Kuntzel, I., Schaap, T., de Vries, A., Bloem, K., Rispens, T., Hoentjen, F., & Derijks, L. J. J. (2023). Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study. European Journal of Drug Metabolism and Pharmacokinetics, 48(4), 377–385. https://doi.org/10.1007/s13318-023-00835-7

Brooks J. T. , Solans B. P. , Lu Y., Kharbanda S., Dvorak C. C. , Lalefar N. , Long S., Gupta A. O., Horn B., Lamba J. K., Huang L., Apsel-Winger B., Keizer R. J., Savic R., Long-Boyle J. (2022). Prospective Validation and Refinement of a Population Pharmacokinetic Model of Fludarabine in Children and Young Adults Undergoing Hematopoietic Cell Transplantation. Pharmaceutics. 14(11):2462. https://doi.org/10.3390/pharmaceutics14112462.

Francke, M. I., Hesselink, D. A., Andrews, L. M., Van Gelder, T., Keizer, R. J., & De Winter, B. C. M. (2022). Model-Based Tacrolimus Follow-Up Dosing in Adult Renal Transplant Recipients: A Simulation Trial. Therapeutic Drug Monitoring, Publish Ahead of Print. https://doi.org/10.1097/FTD.0000000000000979

Brooks, J. T., Keizer, R. J., Long-Boyle, J. R., Kharbanda, S., Dvorak, C. C., & Friend, B. D. (2021). Population Pharmacokinetic Model Development of Tacrolimus in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplantation. Frontiers in Pharmacology, 12, 750672. https://doi.org/10.3389/fphar.2021.750672

Zwart, T. C., de Vries, A. P. J., Engbers, A. G. J., Dam, R. E., van der Boog, P. J. M., Swen, J. J., Keizer, R. J., Dalton, R. N., Guchelaar, H.-J., de Fijter, J. W., & Moes, D. J. A. R. (2021). Model-Based Estimation of Iohexol Plasma Clearance for Pragmatic Renal Function Determination in the Renal Transplantation Setting. Clinical Pharmacokinetics, 60(9), 1201–1215. https://doi.org/10.1007/s40262-021-00998-z

Martial, L. C., Biewenga, M., Ruijter, B. N., Keizer, R., Swen, J. J., Hoek, B., & Moes, D. J. A. R. (2021). Population pharmacokinetics and genetics of oral meltdose tacrolimus (Envarsus) in stable adult liver transplant recipients. British Journal of Clinical Pharmacology, 87(11), 4262–4272. https://doi.org/10.1111/bcp.14842

Apsel Winger, B., Shukla, P., Kharbanda, S., Keizer, R. J., Goswami, S., Cowan, M. J., Dvorak, C. C., & Long-Boyle, J. (2021). The Relationship Between Busulfan Exposure and Achievement of Sustained Donor Myeloid Chimerism in Patients with Non-Malignant Disorders. Transplantation and Cellular Therapy, 27(3), 258.e1-258.e6. https://doi.org/10.1016/j.jtct.2020.12.005

Fors, J., Strydom, N., Fox, W. S., Keizer, R. J., & Savic, R. M. (2020). Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis. PLOS Computational Biology, 16(8), e1008107. https://doi.org/10.1371/journal.pcbi.1008107

Zwart, T. C., Moes, D. J. A. R., van der Boog, P. J. M., van Erp, N. P., de Fijter, J. W., Guchelaar, H.-J., Keizer, R. J., & ter Heine, R. (2021). Model-Informed Precision Dosing of Everolimus: External Validation in Adult Renal Transplant Recipients. Clinical Pharmacokinetics, 60(2), 191–203. https://doi.org/10.1007/s40262-020-00925-8

Morrisette, T., Lodise, T. P., Scheetz, M. H., Goswami, S., Pogue, J. M., & Rybak, M. J. (2020). The Pharmacokinetic and Pharmacodynamic Properties of Hydroxychloroquine and Dose Selection for COVID-19: Putting the Cart Before the Horse. Infectious Diseases and Therapy, 9(3), 561–572. https://doi.org/10.1007/s40121-020-00325-2

Ter Heine, R., Keizer, R. J., van Steeg, K., Smolders, E. J., van Luin, M., Derijks, H. J., de Jager, C. P. C., Frenzel, T., & Brüggemann, R. (2020). Prospective validation of a model-informed precision dosing tool for vancomycin in intensive care patients. British Journal of Clinical Pharmacology, 86(12), 2497–2506. https://doi.org/10.1111/bcp.14360

Frymoyer, A., Schwenk, H. T., Zorn, Y., Bio, L., Moss, J. D., Chasmawala, B., Faulkenberry, J., Goswami, S., Keizer, R. J., & Ghaskari, S. (2020). Model-Informed Precision Dosing of Vancomycin in Hospitalized Children: Implementation and Adoption at an Academic Children’s Hospital. Frontiers in Pharmacology, 11, 551. https://doi.org/10.3389/fphar.2020.00551

Shukla, P., Goswami, S., Keizer, R. J., Winger, B. A., Kharbanda, S., Dvorak, C. C., & Long-Boyle, J. (2020). Assessment of a Model-Informed Precision Dosing Platform Use in Routine Clinical Care for Personalized Busulfan Therapy in the Pediatric Hematopoietic Cell Transplantation (HCT) Population. Frontiers in Pharmacology, 11. https://www.frontiersin.org/articles/10.3389/fphar.2020.00888

Yu, C. Z., Myers, S. R., & Faldasz, J. D. (2020). Simulated Comparison of a Bayesian Clinical Decision Support System Versus Standard of Care For Achieving Gentamicin Pharmacokinetic Targets in Neonates. The Pediatric Infectious Disease Journal, 39(4), 313–317. https://doi.org/10.1097/INF.0000000000002592

Hughes, D. M., Goswami, S., Keizer, R. J., Hughes, M.-S. A., & Faldasz, J. D. (2020). Bayesian clinical decision support-guided versus clinician-guided vancomycin dosing in attainment of targeted pharmacokinetic parameters in a paediatric population. The Journal of Antimicrobial Chemotherapy, 75(2), 434–437. https://doi.org/10.1093/jac/dkz444

van Beek, S. W., Ter Heine, R., Keizer, R. J., Magis-Escurra, C., Aarnoutse, R. E., & Svensson, E. M. (2019). Personalized Tuberculosis Treatment Through Model-Informed Dosing of Rifampicin. Clinical Pharmacokinetics, 58(6), 815–826. https://doi.org/10.1007/s40262-018-00732-2

Frymoyer, A., Stockmann, C., Hersh, A. L., Goswami, S., & Keizer, R. J. (2019). Individualized Empiric Vancomycin Dosing in Neonates Using a Model-Based Approach. Journal of the Pediatric Infectious Diseases Society, 8(2), 97–104. https://doi.org/10.1093/jpids/pix109

Bartelink, I. H., Lalmohamed, A., van Reij, E. M. L., Dvorak, C. C., Savic, R. M., Zwaveling, J., Bredius, R. G. M., Egberts, A. C. G., Bierings, M., Kletzel, M., Shaw, P. J., Nath, C. E., Hempel, G., Ansari, M., Krajinovic, M., Théorêt, Y., Duval, M., Keizer, R. J., Bittencourt, H., … Boelens, J. J. (2016). Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. The Lancet Haematology, 3(11), e526–e536. https://doi.org/10.1016/S2352-3026(16)30114-4