ArticleBiopharmaceutics & drug disposition2015
Effects of hypertonic buffer composition on lymph node uptake and bioavailability of rituximab, after subcutaneous administration.
Article in Biopharmaceutics & drug disposition, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Comparison of efficacy between subcutaneous and intravenous application of moss-aGal in the mouse model of Fabry disease.JIMD reports · 2023Article
- Review
- A Two-Pore Physiologically Based Pharmacokinetic Model to Predict Subcutaneously Administered Different-Size Antibody/Antibody Fragments.The AAPS journal · 2021Article
- Machine Learning Attempts for Predicting Human Subcutaneous Bioavailability of Monoclonal Antibodies.Pharmaceutical research · 2021Article
- Proteolysis and Oxidation of Therapeutic Proteins After Intradermal or Subcutaneous Administration.Journal of pharmaceutical sciences · 2020Review
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Pharmacokinetic and Pharmacodynamic Properties of Drug Delivery Systems.The Journal of pharmacology and experimental therapeutics · 2019Review
- Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins.Journal of pharmaceutical sciences · 2018Review
- Fluid Osmolarity Acutely and Differentially Modulates Lymphatic Vessels Intrinsic Contractions and Lymph Flow.Frontiers in physiology · 2018Article
- Optimizing the Bioavailability of Subcutaneously Administered Biotherapeutics Through Mechanochemical Drivers.Pharmaceutical research · 2017Review
- Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.Journal of pharmacokinetics and pharmacodynamics · 2015Review
- Anatomical, physiological, and experimental factors affecting the bioavailability of sc-administered large biotherapeutics.Journal of pharmaceutical sciences · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The subcutaneous administration of biologics is highly desirable; however, incomplete bioavailability after s.c. administration remains a major challenge. In this work we investigated the effects of excipient dependent hyperosmolarity on lymphatic uptake and plasma exposure of rituximab as a model protein. Using Swiss Webster (SW) mice as the animal model, we compared the effects of NaCl, mannitol and O-phospho-L-serine (OPLS) on the plasma concentration of rituximab over 5 days after s.c. administration. An increase was observed in plasma concentrations in animals administered rituximab in hypertonic buffer solutions, compared with isotonic buffer. Bioavailability, as estimated by our pharmacokinetic model, increased from 29% in isotonic buffer to 54% in hypertonic buffer containing NaCl, to almost complete bioavailability in hypertonic buffers containing high dose OPLS or mannitol. This improvement in plasma exposure is due to the improved lymphatic trafficking as evident from the increase in the fraction of dose trafficked through the lymph nodes in the presence of hypertonic buffers. The fraction of the dose trafficked through the lymphatics, as estimated by the model, increased from 0.05% in isotonic buffer to 13% in hypertonic buffer containing NaCl to about 30% for hypertonic buffers containing high dose OPLS and mannitol. The data suggest that hypertonic solutions may be a viable option for improving s.c. bioavailability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.