ArticlePharmaceutical research2006
The absorption of darbepoetin alfa occurs predominantly via the lymphatics following subcutaneous administration to sheep.
Article in Pharmaceutical research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 38 citations in OpenAlex.
- An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males.British journal of clinical pharmacology · 2010Trial
- A Dendrimer Peptide (KK2DP7) Delivery System with Dual Functions of Lymph Node Targeting and Immune Adjuvants as a General Strategy for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment.Molecular pharmaceutics · 2022Article
- Nanoparticle-based approaches to target the lymphatic system for antitumor treatment.Cellular and molecular life sciences : CMLS · 2021Review
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Addition of 20-kDa PEG to Insulin Lispro Alters Absorption and Decreases Clearance in Animals.Pharmaceutical research · 2016Article
- A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity.Bioconjugate chemistry · 2016Article
- A Bottom-Up Whole-Body Physiologically Based Pharmacokinetic Model to Mechanistically Predict Tissue Distribution and the Rate of Subcutaneous Absorption of Therapeutic Proteins.The AAPS journal · 2016Article
- Protection against SHIV Challenge by Subcutaneous Administration of the Plant-Derived PGT121 Broadly Neutralizing Antibody in Macaques.PloS one · 2016Article
- From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity.Nature reviews. Drug discovery · 2015Review
- In vivo fluorescence imaging of IgG1 aggregates after subcutaneous and intravenous injection in mice.Pharmaceutical research · 2014Article
- Clinical pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents.Clinical pharmacokinetics · 2013Review
- Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies.Clinical pharmacokinetics · 2013Review
- Mechanistic determinants of biotherapeutics absorption following SC administration.The AAPS journal · 2012Review
- Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats.Pharmaceutical research · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo determine the contribution of the lymphatics to the systemic availability of darbepoetin alfa (DA) using an established sheep model. MATERIALS AND
methodsDA was administered either by intravenous (IV) injection (0.2, 0.5 or 2 microg/kg) or by subcutaneous (SC) administration (2 microg/kg) into the interdigital space of the hind leg. A SC control group was used to determine the absolute bioavailability (F (sys)). Cannulation of the peripheral lymphatics in a parallel SC group allowed the continuous collection of lymph draining the injection site and determination of the cumulative amount of DA absorbed via the lymphatics. Serum and lymph concentrations of DA were determined by ELISA. The fraction of the dose absorbed into the lymphatics (F (lymph)) relative to the fraction absorbed directly into the blood (F (blood)) was determined using a compartmental approach.
resultsDose-linear pharmacokinetics was observed within the dose range investigated. The bioavailability was virtually complete following SC injection into the interdigital space (88.4 +/- 15.7%). A high proportion of the administered dose was recovered in peripheral lymph (90.2 +/- 4.4%) resulting in a substantial reduction in the systemic availability in lymph cannulated animals (3.7%).
conclusionThe high recovery of DA in the peripheral lymph demonstrated near complete absorption of this recombinant protein via the lymphatics in a lymph cannulated sheep model.
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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.