The lymphatic system plays a major role in the intravenous and subcutaneous pharmacokinetics of trastuzumab in rats

Molecular Pharmaceutics
Annette M DahlbergMichelle P McIntosh

Abstract

Therapeutic monoclonal antibodies are currently delivered mainly via the intravenous route, since large volumes are often required to deliver a therapeutic dose. Administration via the subcutaneous route would have several therapeutic advantages; the absorption mechanisms for antibodies dosed subcutaneously are poorly understood. This study was conducted to develop a better understanding of the mechanisms governing the subcutaneous absorption and trafficking of monoclonal antibodies. Specifically, the role of the lymphatic system in the absorption and prolonged plasma exposure of trastuzumab was explored in thoracic lymph duct-cannulated rats after SC and IV dosing. A population pharmacokinetic model was developed in S-ADAPT to simultaneously fit all plasma and lymph concentrations and to predict the pharmacokinetics in nonlymph duct-cannulated animals. The estimated absolute bioavailability of trastuzumab after SC administration in rats was 85.5%. Following SC administration, 53.1% of the trastuzumab dose was absorbed via a first-order process (mean absorption time: 99.6 h) into the peripheral lymph compartment and 32.4% of the dose was absorbed by a Michaelis-Menten process into the central compartment. Recovery in thoracic l...Continue Reading

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·P CarterH M Shepard
Aug 6, 1998·Annals of Hematology·J E GessnerR E Schmidt
Aug 8, 2001·Advanced Drug Delivery Reviews·C Oussoren, G Storm
Feb 24, 2006·The New England Journal of Medicine·Heikki JoensuuUNKNOWN FinHer Study Investigators
Sep 19, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jagannath KotaSusan A Charman
Aug 19, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lisa M KaminskasChristopher Jh Porter
Sep 8, 2010·Clinical Pharmacokinetics·Nathanael L Dirks, Bernd Meibohm
Mar 4, 2011·The AAPS Journal·Jurgen Bernd BulittaCornelia Barbara Landersdorfer
Nov 7, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Leonid Kagan, Donald E Mager
Dec 18, 2012·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Lincan DuanGaofeng Li
Mar 19, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lisa M KaminskasChristopher J H Porter
Apr 1, 2005·Drug Discovery Today. Technologies·Danielle N McLennanSusan A Charman

❮ Previous
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Citations

Oct 17, 2015·Nature Reviews. Drug Discovery·Natalie L TrevaskisChristopher J H Porter
Feb 5, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Elliot Offman, Andrea N Edginton
Jun 6, 2017·Small·Debora BonvinMarijana Mionić Ebersold
May 29, 2018·Expert Opinion on Drug Metabolism & Toxicology·Paul Malik, Andrea Edginton
Feb 19, 2019·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·D PaniaguaA Alagón
Feb 28, 2019·European Journal of Drug Metabolism and Pharmacokinetics·Tomasz GrabowskiAnna Chełmońska-Soyta
Aug 8, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wolfgang F Richter, Björn Jacobsen
Aug 15, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Leonid Kagan
Dec 11, 2019·Antibodies·Veena A Thomas, Joseph P Balthasar
Jan 20, 2021·British Journal of Clinical Pharmacology·Stefania KokkaliJean-Emmanuel Kurtz
Mar 17, 2020·Critical Reviews in Oncology/hematology·Antonino MusolinoMaria Michiara
Jan 18, 2018·Journal of Pharmaceutical Sciences·Michael R Turner, Sathy V Balu-Iyer
Jul 30, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fudan ZhengTonglei Li
May 11, 2019·ACS Applied Materials & Interfaces·He HuNicole F Steinmetz
Sep 7, 2021·Frontiers in Pharmacology·Serena VanAmanda J Stolarz

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