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Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products
- As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination isAs a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.…
Verfasserangaben: | Karin WeisserGND, Sabine StüblerORCiDGND, Walter Matheis, Wilhelm HuisingaORCiDGND |
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DOI: | https://doi.org/10.1016/j.yrtph.2017.02.018 |
ISSN: | 0273-2300 |
ISSN: | 1096-0295 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28237896 |
Titel des übergeordneten Werks (Englisch): | Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology |
Verlag: | Elsevier |
Verlagsort: | San Diego |
Publikationstyp: | Sonstiges |
Sprache: | Englisch |
Datum der Erstveröffentlichung: | 22.02.2017 |
Erscheinungsjahr: | 2017 |
Datum der Freischaltung: | 12.04.2022 |
Freies Schlagwort / Tag: | Absorption kinetics; Aluminium; Aluminium adjuvants; In vitro dissolution; Toxicokinetic modelling |
Band: | 88 |
Seitenanzahl: | 12 |
Erste Seite: | 310 |
Letzte Seite: | 321 |
Fördernde Institution: | German Ministry of Health [ZMVI1-2515-FSB-772] |
Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Mathematik |
Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie | |
DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 51 Mathematik / 510 Mathematik |
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie | |
Peer Review: | Referiert |