Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability
Background/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacok...
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2024-12-01
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| author | Marija Jovanović Ana Homšek Srđan Marković Đorđe Kralj Petar Svorcan Tamara Knežević Ivanovski Olga Odanović Katarina Vučićević |
| author_facet | Marija Jovanović Ana Homšek Srđan Marković Đorđe Kralj Petar Svorcan Tamara Knežević Ivanovski Olga Odanović Katarina Vučićević |
| author_sort | Marija Jovanović |
| collection | DOAJ |
| description | Background/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications. |
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| id | doaj-art-458f0f38724c4a2a9eca7e858dd8515b |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-458f0f38724c4a2a9eca7e858dd8515b2025-01-24T13:23:49ZengMDPI AGBiomedicines2227-90592024-12-011314310.3390/biomedicines13010043Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical ApplicabilityMarija Jovanović0Ana Homšek1Srđan Marković2Đorđe Kralj3Petar Svorcan4Tamara Knežević Ivanovski5Olga Odanović6Katarina Vučićević7Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, SerbiaDepartment of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, SerbiaDepartment of Gastroenterology and Hepatology, University Hospital Medical Center “Zvezdara”, 11000 Belgrade, SerbiaDepartment of Gastroenterology and Hepatology, University Hospital Medical Center “Zvezdara”, 11000 Belgrade, SerbiaDepartment of Gastroenterology and Hepatology, University Hospital Medical Center “Zvezdara”, 11000 Belgrade, SerbiaDepartment of Gastroenterology and Hepatology, University Hospital Medical Center “Zvezdara”, 11000 Belgrade, SerbiaDepartment of Gastroenterology and Hepatology, University Hospital Medical Center “Zvezdara”, 11000 Belgrade, SerbiaDepartment of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, SerbiaBackground/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications.https://www.mdpi.com/2227-9059/13/1/43predictive performancesimulationsprediction errorNONMEMvedolizumabpharmacokinetics |
| spellingShingle | Marija Jovanović Ana Homšek Srđan Marković Đorđe Kralj Petar Svorcan Tamara Knežević Ivanovski Olga Odanović Katarina Vučićević Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability Biomedicines predictive performance simulations prediction error NONMEM vedolizumab pharmacokinetics |
| title | Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability |
| title_full | Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability |
| title_fullStr | Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability |
| title_full_unstemmed | Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability |
| title_short | Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability |
| title_sort | review and external evaluation of population pharmacokinetic models for vedolizumab in patients with inflammatory bowel disease assessing predictive performance and clinical applicability |
| topic | predictive performance simulations prediction error NONMEM vedolizumab pharmacokinetics |
| url | https://www.mdpi.com/2227-9059/13/1/43 |
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