Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

Autor:	Pertinez H; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Kaushik A; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21287, USA., Curley P; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Arshad U; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., El-Khateeb E; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Li SY; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21287, USA., Tasneen R; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21287, USA., Sharp J; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Kijak E; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Herriott J; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Neary M; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Noë M; Department of Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands., Flexner C; Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA., Nuermberger E; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21287, USA., Owen A; Center of Excellence for Long-Acting Technologies (CELT), William Henry Duncan Building, University of Liverpool, Crown Street, Liverpool L7 8TX, UK.; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, William Henry Duncan Building, Crown Street, Liverpool L69 7BE, UK., Ammerman NC; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, 1550 Orleans Street, Baltimore, MD, 21287, USA.; Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 06. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1101/2024.03.03.583160
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu