Therapeutic drug monitoring of monoclonal antibodies: Applicability based on their pharmacokinetic properties |
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| Affiliation: | 1. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, 14214 United States;2. Department of Pharmacology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104 United States;1. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan;2. The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan;3. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan;4. Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei, Taiwan;5. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan;6. Department of Medical Oncology, National Taiwan University Cancer Center Hospital, Taipei, Taiwan;7. Stroke Center and Department of Neurology, National Taiwan University Hospital, Taiwan;8. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan;1. Department of Clinical Pharmacy, Division of Laboratory Medicine and Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands;2. Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands;3. Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands;1. Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek/The Netherlands Cancer Institute, Amsterdam, The Netherlands;2. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands;3. Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands;4. Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Department of Pharmaceutical Sciences, Utrecht University, The Netherlands |
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| Abstract: | Monoclonal antibodies (mAbs) have dramatically improved clinical outcomes for inflammatory and malignant diseases. The elimination route of mAbs is cellular uptake by nonspecific pinocytosis or receptor-mediated endocytosis followed by proteolytic degradation which is protected by neonatal Fc-receptor or mediated by antigenic target. There is a wide-interindividual variability in mAbs exposure due to target burden and other factors affecting unique their pharmacokinetics. It has been reported that higher exposures are correlated with better clinical outcomes of various therapeutic mAbs. On the other hand, flat exposure-efficacy relationships of anti-PD-1 antibodies nivolmab and pembrolizumab mean ensuring absolute maximum efficacy in each patient by the approved dose regardless of their large interpatient variability in pharmacokinetics. Administration of mAbs can induce production of anti-drug antibodies (ADAs), which impact on their pharmacokinetics and pharmacodynamics. In therapeutic drug monitoring (TDM) of mAbs, when total (free, soluble target bound and ADAs bound) mAbs concentration is measured, ADAs content (concentration/titer) should be also monitored because mAbs exists in inactive complex with ADAs. Along with determination of appropriated therapeutic windows taking into account ADAs content, treatment algorithms for TDM-guided clinical decision-making must be developed and prospectively shown to be superior to traditional clinical care for each mAb in each indication. |
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| Keywords: | Anti-drug antibody Exposure-response relationship Cancer Inflammatory disease Malignant disease Monoclonal antibody Therapeutic drug monitoring |
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