{"doi":"10.1101/2024.03.03.583160","title":"Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488073,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":374333,"name":"Amit Kaushik","orcid":"0000-0002-5622-1721","position":1,"is_corresponding":false},{"id":254187,"name":"Paul Curley","orcid":"0000-0003-4596-2708","position":2,"is_corresponding":false},{"id":254184,"name":"Usman Arshad","orcid":"0000-0003-1586-1885","position":3,"is_corresponding":false},{"id":1332590,"name":"Eman El‐Khateeb","orcid":"0000-0002-8365-6528","position":4,"is_corresponding":false},{"id":576642,"name":"Si‐Yang Li","orcid":null,"position":5,"is_corresponding":false},{"id":343027,"name":"Rokeya Tasneen","orcid":null,"position":6,"is_corresponding":false},{"id":254189,"name":"Joanne Sharp","orcid":"0000-0001-8482-5736","position":7,"is_corresponding":false},{"id":985074,"name":"Edyta Kijak","orcid":null,"position":8,"is_corresponding":false},{"id":984591,"name":"Joanne Herriott","orcid":"0000-0002-4938-7555","position":9,"is_corresponding":false},{"id":254188,"name":"Megan Neary","orcid":"0000-0002-4960-2139","position":10,"is_corresponding":false},{"id":262910,"name":"Michaël Noë","orcid":"0000-0002-5336-4508","position":11,"is_corresponding":false},{"id":498021,"name":"Charles Flexner","orcid":"0000-0002-4495-5349","position":12,"is_corresponding":false},{"id":291391,"name":"Eric L. Nuermberger","orcid":"0000-0003-1440-9889","position":13,"is_corresponding":false},{"id":254201,"name":"Andrew Owen","orcid":"0000-0002-9819-7651","position":14,"is_corresponding":false},{"id":584729,"name":"Nicole C. Ammerman","orcid":"0000-0001-9359-9144","position":15,"is_corresponding":false},{"id":256856,"name":"Henry Pertinez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:08:15.008850Z","pmid":"38496644","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}