Pharmacokinetics and biodistribution of squalene-containing emulsion adjuvant following intramuscular injection of H5N1 influenza vaccine in mice
| Autor: | Michelle Vanlandingham, Linda S. Von Tungeln, Robert J. Mitkus, Richard A. Forshee, Frederick A. Beland, Steven A. Anderson, Million A. Tegenge |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Squalene Pathology medicine.medical_specialty Metabolic Clearance Rate medicine.medical_treatment Population MF59 Cmax Polysorbates Pharmacology Toxicology Injections Intramuscular Models Biological Risk Assessment 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Adjuvants Immunologic medicine Animals Computer Simulation Tissue Distribution 030212 general & internal medicine AS03 education education.field_of_study Mice Inbred BALB C Influenza A Virus H5N1 Subtype business.industry General Medicine Toxicokinetics 030104 developmental biology chemistry Nonlinear Dynamics Influenza Vaccines Area Under Curve Emulsions Female Intramuscular injection business Adjuvant Half-Life |
| Zdroj: | Regulatory toxicology and pharmacology : RTP. 81 |
| ISSN: | 1096-0295 |
| Popis: | Squalene is a component of oil-in-water emulsion adjuvants developed for potential use in some influenza vaccines. The biodistribution of the squalene-containing emulsion adjuvant (AddaVax™) alone and as part of complete H5N1 vaccine was quantified in mechanistically and toxicologically relevant target tissues up to 336 h (14 days) following injection into quadriceps muscle. At 1 h, about 55% of the intramuscularly injected dose of squalene was detected in the local quadriceps muscles and this decreased to 26% at 48 h. Twenty-four hours after the injection, approximately 5%, 1%, and 0.6% of the injected dose was detected in inguinal fat, draining lymph nodes, and sciatic nerve, respectively. The peak concentration for kidney, brain, spinal cord, bone marrow, and spleen was each less than 1% of the injected dose, and H5N1 antigen did not significantly alter the biodistribution of squalene to these tissues. The area-under-blood-concentration curve (AUC) and peak blood concentration (Cmax) of squalene were slightly higher (20–25%) in the presence of H5N1 antigen. A population pharmacokinetic model-based statistical analysis identified body weight and H5N1 antigen as covariates influencing the clearance of squalene. The results contribute to the body of knowledge informing benefit-risk analyses of squalene-containing emulsion vaccine adjuvants. |
| Databáze: | OpenAIRE |
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