ArticlePharmaceutical research2012
Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 102 citations in OpenAlex.
- Hyaluronidase-enhanced subcutaneous delivery of bNAbs: a phase 1 randomized controlled clinical trial in HIV-uninfected women.Nature communications · 2025Trial
- Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase.British journal of cancer · 2013Trial
- A Review on Lymphatic Uptake of Large Therapeutic Proteins after Subcutaneous Injection.Pharmaceutical research · 2026Review
- Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cross-Species Extrapolation of Neonatal Fc Receptor (FcRn) Binding Affinity to Predict Monoclonal Antibody Pharmacokinetics in Humans Using Physiologically Based Pharmacokinetic Modeling (PBPK): Are We There Yet?ACS pharmacology & translational science · 2025Article
- Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats.Nature communications · 2025Article
- A Semi-Mechanistic Mathematical Model of Immune Tolerance Induction to Support Preclinical Studies of Human Monoclonal Antibodies in Rats.Pharmaceutics · 2025Article
- Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.Pharmaceutical research · 2025Article
- Rat as a Predictive Model for Human Clearance and Bioavailability of Monoclonal Antibodies.Antibodies (Basel, Switzerland) · 2024Article
- Mim8, a novel factor VIIIa mimetic bispecific antibody, shows favorable safety and pharmacokinetics in healthy adults.Research and practice in thrombosis and haemostasis · 2023Article
- An Analytical Solution for Saturable Absorption in Pharmacokinetics Models.Pharmaceutical research · 2023Article
- Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights.Frontiers in oncology · 2023Review
- Ustekinumab pharmacokinetics after subcutaneous administration in swine model.Journal of veterinary science · 2021Article
- Machine Learning Attempts for Predicting Human Subcutaneous Bioavailability of Monoclonal Antibodies.Pharmaceutical research · 2021Article
- Article
- Development of a Pharmacokinetic Model Describing Neonatal Fc Receptor-Mediated Recycling of HL2351, a Novel Hybrid Fc-Fused Interleukin-1 Receptor Antagonist, to Optimize Dosage Regimen.CPT: pharmacometrics & systems pharmacology · 2020Article
- Blockade of immune checkpoints in lymph nodes through locoregional delivery augments cancer immunotherapy.Science translational medicine · 2020Article
- Lymphatic Distribution of Etanercept Following Intravenous and Subcutaneous Delivery to Rats.Pharmaceutical research · 2020Article
- 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
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine the effect of dose, the anatomical site of injection, and the injection volume on subcutaneous absorption of rituximab in rats and to explore absorption mechanisms using pharmacokinetic modeling.
methodsRituximab serum concentrations were measured following intravenous and subcutaneous administration at the back, abdomen, and foot of rats. Several pharmacokinetic models were developed that included linear and saturable absorption, and degradation and/or protective binding at the injection site.
resultsRituximab exhibited linear kinetics following intravenous administration; however, bioavailability following subcutaneous injection was inversely related to the dose level. For the 1 mg/kg dose, bioavailability was approximately 70% at all tested injection sites, with faster absorption from the foot (T(max) = 12 h for foot vs. 4.6 days for back). Bioavailability for the 10 mg/kg dose was 44 and 31% for the abdomen and back sites and 18% for 40 mg/kg injected at the back. A pharmacokinetic model that included binding as part of the absorption mechanism successfully captured the nonlinearities in rituximab absorption.
conclusionThe anatomical site of subcutaneous injection influences the rate of absorption and bioavailability of rituximab in rats. Saturable binding may be a major determinant of the nonlinear absorptive transport of monoclonal antibodies.
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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.