Pharmacometabolomics Enables Real-World Drug Metabolism Sciences
<b>Background/Objectives</b>: Pharmacogenomics (PGx) has revolutionized personalized medicine, notably by predicting drug responses through the study of the metabolic genotype of drug-metabolizing enzymes. However, these genotypes rely heavily on the availability and completeness of drug...
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| author | Fleur B. Nijdam Marieke A. J. Hof Hans Blokzijl Stephan J. L. Bakker Eelko Hak Gérard Hopfgartner Frank Klont on behalf of the TransplantLines Investigators |
| author_facet | Fleur B. Nijdam Marieke A. J. Hof Hans Blokzijl Stephan J. L. Bakker Eelko Hak Gérard Hopfgartner Frank Klont on behalf of the TransplantLines Investigators |
| author_sort | Fleur B. Nijdam |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Pharmacogenomics (PGx) has revolutionized personalized medicine, notably by predicting drug responses through the study of the metabolic genotype of drug-metabolizing enzymes. However, these genotypes rely heavily on the availability and completeness of drug metabolism information and do not account for (all) “phenoconversion” factors, like drug–drug interactions and comorbidities. To address these limitations, a more phenotypic approach would be desirable, for which pharmacometabolomics (PMx) could be useful by studying and elucidating drug metabolism in patient samples, such as blood and urine. <b>Methods</b>: This study explored the potential of PMx to analyze real-world drug metabolite profiles of the extensively studied drug cyclosporine (CsA) using 24-h urine samples from 732 kidney and 350 liver transplant recipients included in the TransplantLines Biobank and Cohort Study (NCT identifier NCT03272841). Detected metabolites were matched with existing information on CsA metabolism gathered through a comprehensive literature review, aiming to confirm previously reported metabolites and identify potentially unreported ones. <b>Results</b>: Our analyses confirmed the urinary presence of CsA and six known metabolites. Additionally, we detected three known metabolites not previously reported in urine and identified one unreported metabolite, potentially suggesting the involvement of glutathione conjugation. Lastly, the observed metabolic patterns showed no notable differences between kidney and liver transplant recipients. <b>Conclusions</b>: Our findings demonstrate the potential of PMx to enhance the understanding of drug metabolism, even for well-studied compounds such as CsA. Moreover, this study highlights the value of PMx in real-world drug metabolism research and its potential to complement PGx in advancing personalized medicine. |
| format | Article |
| id | doaj-art-404ab00824064b409fc833e16536a356 |
| institution | Kabale University |
| issn | 2218-1989 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj-art-404ab00824064b409fc833e16536a3562025-01-24T13:41:15ZengMDPI AGMetabolites2218-19892025-01-011513910.3390/metabo15010039Pharmacometabolomics Enables Real-World Drug Metabolism SciencesFleur B. Nijdam0Marieke A. J. Hof1Hans Blokzijl2Stephan J. L. Bakker3Eelko Hak4Gérard Hopfgartner5Frank Klont6on behalf of the TransplantLines Investigators7Unit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsDepartment of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsDepartment of Gastroenterology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The NetherlandsDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The NetherlandsUnit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsLife Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva, SwitzerlandUnit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The NetherlandsGroup of Authors on Behalf of the Transplant Lines Biobank and Cohort Study, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands<b>Background/Objectives</b>: Pharmacogenomics (PGx) has revolutionized personalized medicine, notably by predicting drug responses through the study of the metabolic genotype of drug-metabolizing enzymes. However, these genotypes rely heavily on the availability and completeness of drug metabolism information and do not account for (all) “phenoconversion” factors, like drug–drug interactions and comorbidities. To address these limitations, a more phenotypic approach would be desirable, for which pharmacometabolomics (PMx) could be useful by studying and elucidating drug metabolism in patient samples, such as blood and urine. <b>Methods</b>: This study explored the potential of PMx to analyze real-world drug metabolite profiles of the extensively studied drug cyclosporine (CsA) using 24-h urine samples from 732 kidney and 350 liver transplant recipients included in the TransplantLines Biobank and Cohort Study (NCT identifier NCT03272841). Detected metabolites were matched with existing information on CsA metabolism gathered through a comprehensive literature review, aiming to confirm previously reported metabolites and identify potentially unreported ones. <b>Results</b>: Our analyses confirmed the urinary presence of CsA and six known metabolites. Additionally, we detected three known metabolites not previously reported in urine and identified one unreported metabolite, potentially suggesting the involvement of glutathione conjugation. Lastly, the observed metabolic patterns showed no notable differences between kidney and liver transplant recipients. <b>Conclusions</b>: Our findings demonstrate the potential of PMx to enhance the understanding of drug metabolism, even for well-studied compounds such as CsA. Moreover, this study highlights the value of PMx in real-world drug metabolism research and its potential to complement PGx in advancing personalized medicine.https://www.mdpi.com/2218-1989/15/1/39personalized medicinepharmacogenomicspharmacometabolomicsreal-worlddrug metabolismhuman |
| spellingShingle | Fleur B. Nijdam Marieke A. J. Hof Hans Blokzijl Stephan J. L. Bakker Eelko Hak Gérard Hopfgartner Frank Klont on behalf of the TransplantLines Investigators Pharmacometabolomics Enables Real-World Drug Metabolism Sciences Metabolites personalized medicine pharmacogenomics pharmacometabolomics real-world drug metabolism human |
| title | Pharmacometabolomics Enables Real-World Drug Metabolism Sciences |
| title_full | Pharmacometabolomics Enables Real-World Drug Metabolism Sciences |
| title_fullStr | Pharmacometabolomics Enables Real-World Drug Metabolism Sciences |
| title_full_unstemmed | Pharmacometabolomics Enables Real-World Drug Metabolism Sciences |
| title_short | Pharmacometabolomics Enables Real-World Drug Metabolism Sciences |
| title_sort | pharmacometabolomics enables real world drug metabolism sciences |
| topic | personalized medicine pharmacogenomics pharmacometabolomics real-world drug metabolism human |
| url | https://www.mdpi.com/2218-1989/15/1/39 |
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