Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models
A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations. The objective of this pilot study was to evaluate the impact of co-administration of hyaluronidase on the drug release kinetics, pharmacokinetic profiles, and injection site histopathology of the long-acting injectable paliperidone palmitate for up to four weeks following intramuscular injection in mouse and rat models. In both species, co-administration of hyaluronidase increased paliperidone plasma exposures the first week after injection but did not negate the overall long-acting release nature of the formulation. Hyaluronidase-associated modification of the injection site depot was observed in mice but not in rats. These findings suggest that further investigation of hyaluronidase with long-acting injectable agents is warranted.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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Enthalten in: |
bioRxiv : the preprint server for biology - (2024) vom: 06. März |
Sprache: |
Englisch |
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Beteiligte Personen: |
Pertinez, Henry [VerfasserIn] |
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Links: |
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Themen: |
Histopathology |
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Anmerkungen: |
Date Revised 25.03.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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doi: |
10.1101/2024.03.03.583160 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM369863305 |
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520 | |a A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations. The objective of this pilot study was to evaluate the impact of co-administration of hyaluronidase on the drug release kinetics, pharmacokinetic profiles, and injection site histopathology of the long-acting injectable paliperidone palmitate for up to four weeks following intramuscular injection in mouse and rat models. In both species, co-administration of hyaluronidase increased paliperidone plasma exposures the first week after injection but did not negate the overall long-acting release nature of the formulation. Hyaluronidase-associated modification of the injection site depot was observed in mice but not in rats. These findings suggest that further investigation of hyaluronidase with long-acting injectable agents is warranted | ||
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700 | 1 | |a Kaushik, Amit |e verfasserin |4 aut | |
700 | 1 | |a Curley, Paul |e verfasserin |4 aut | |
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700 | 1 | |a El-Khateeb, Eman |e verfasserin |4 aut | |
700 | 1 | |a Li, Si-Yang |e verfasserin |4 aut | |
700 | 1 | |a Tasneen, Rokeya |e verfasserin |4 aut | |
700 | 1 | |a Sharp, Joanne |e verfasserin |4 aut | |
700 | 1 | |a Kijak, Edyta |e verfasserin |4 aut | |
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700 | 1 | |a Nuermberger, Eric |e verfasserin |4 aut | |
700 | 1 | |a Owen, Andrew |e verfasserin |4 aut | |
700 | 1 | |a Ammerman, Nicole C |e verfasserin |4 aut | |
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