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Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration

  • Review Article
  • Theme: ADME of Therapeutic Proteins
  • Published:
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Abstract

The subcutaneous (SC) route is of growing interest for the administration of biotherapeutics. Key products on the biotherapeutic market such as insulins, but also several immunoglobulins or Fc-fusion proteins, are administered SC. Despite the importance of the SC route, the available knowledge about the processes involved in the SC absorption of biotherapeutics is limited. This review summarizes available information on the physiology of the SC tissue and on the pharmacokinetic processes after SC administration including “first pass catabolism” at the administration site as well as transport in the extracellular matrix of the SC tissue, followed by absorption into the blood circulation or the lymphatic system. Both monoclonal antibodies and other biotherapeutics are discussed. Determinants of absorption after SC administration are summarized including compound properties such as charge or molecular weight. Scale-up of animal data to humans is discussed, including the current shortcomings of empirical scaling approaches and the lack of suitable mechanistic approaches.

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ACKNOWLEDGMENTS

This study was supported in part by the Center for Protein Therapeutics, University at Buffalo, State University of New York (for MEM). The authors thank Elke Atzpodien, F. Hoffmann-La Roche, Basel, for providing the section of rat skin.

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Authors and Affiliations

  1. Non-clinical Safety, Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, 4070, Basel, Switzerland

    Wolfgang F. Richter

  2. Clinical PKPD, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, 07936, USA

    Suraj G. Bhansali

  3. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Amherst, New York, 14260, USA

    Marilyn E. Morris

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  1. Wolfgang F. Richter
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  3. Marilyn E. Morris
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Correspondence to Marilyn E. Morris.

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Guest Editors: Craig Svensson, Joseph Balthasar, and Frank-Peter Theil

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Richter, W.F., Bhansali, S.G. & Morris, M.E. Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration. AAPS J 14, 559–570 (2012). https://doi.org/10.1208/s12248-012-9367-0

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