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Fluctuations in Pharmacokinetics Profiles of Monoclonal Antibodies

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Monoclonal antibodies (mAbs) are a group of drugs with predicted slow linear and target-mediated distribution and elimination. Visual inspection of published pharmacokinetic profiles of mAbs frequently reveals plateaus in the distribution phase or an increasing concentration many days after a single intravenous dose. A question which has been left unanswered until now is whether mAbs undergo recirculation mechanisms. If so, then which mechanisms are crucial for the fluctuation in their pharmacokinetics profiles? What is the impact of such mechanisms on mAb absorption, distribution and elimination? Current commentary accounts for the fluctuation of mAbs concentrations based on different mechanisms, as well in different phases of their in vivo disposition. Current knowledge shows significant impact of mAbs lymphatic recirculation on characteristics of their pharmacokinetics profiles. Fluctuating or plateau phases in pharmacokinetic profiles of mAbs are a consequence of multiple simultaneously occurring recirculatory as well as adsorption/desorption processes rather than only slow, continuous elimination. Lymphatic recirculation as well as other mechanisms appears to be an obvious element of the mAbs disposition. Periodic changes in the key factors affecting mAbs disposition can be responsible for the unpredictable concentration peaks in absorption, distribution and the elimination phase.

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Acknowledgements

Authors would like to express great appreciation to Neil Johnson Ph.D. for his professional guidance and valuable support in manuscript preparation.

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Authors and Affiliations

  1. Polpharma Biologics SA, Trzy lipy 3, 80-172, Gdańsk, Poland

    Tomasz Grabowski

  2. Centre for Human Drug Research, Zernikedreef 8, 2333 CL, Leiden, The Netherlands

    Joannes A. A. Reijers

  3. Department of Pharmacology, Faculty of Veterinary Medicine, University of Life Sciences, Akademicka 12, 20-033, Lublin, Poland

    Artur Burmańczuk

  4. Laboratory of Reproductive Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

    Anna Chełmońska-Soyta

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  1. Tomasz Grabowski
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  2. Joannes A. A. Reijers
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  4. Anna Chełmońska-Soyta
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Correspondence to Tomasz Grabowski.

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Funding

Tomasz Grabowski declare that his contribution in manuscript was related to financial support of The National Centre for Research and Development in Poland, Grant Number: POIR.01.02.00-00-0016/17.

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The authors declare that they have no conflict of interest.

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Grabowski, T., Reijers, J.A.A., Burmańczuk, A. et al. Fluctuations in Pharmacokinetics Profiles of Monoclonal Antibodies. Eur J Drug Metab Pharmacokinet 44, 585–589 (2019). https://doi.org/10.1007/s13318-019-00548-w

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  • DOI: https://doi.org/10.1007/s13318-019-00548-w

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