Volume 89, Issue 2 pp. 168-177
Research Article

Systemic availability and lymphatic transport of human growth hormone administered by subcutaneous injection

Susan A. Charman

Corresponding Author

Susan A. Charman

Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia

Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, AustraliaSearch for more papers by this author
Alicia M. Segrave

Alicia M. Segrave

Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia

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Glenn A. Edwards

Glenn A. Edwards

Department of Veterinary Sciences, The University of Melbourne, Werribee, Victoria, 3030, Australia

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Christopher J.H. Porter

Christopher J.H. Porter

Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia

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Abstract

Degradation of human growth hormone (hGH) at the injection site has previously been implicated as the basis for its reduced systemic availability following subcutaneous (SC) administration. The goal of these studies was to develop an animal model which would allow mass balance calculations to (i) quantify the loss at the injection site and (ii) determine the role of the lymphatics in the transport of subcutaneously-administered hGH. The animal model utilized a sheep and enabled simultaneous sampling of blood and collection of either peripheral lymph (via the efferent duct of the popliteal lymph node draining the injection site) or central lymph (via the thoracic lymph duct). In non-lymph cannulated sheep, the systemic availability of hGH following SC dosing was 58.4 ± 9.1% (mean ± SEM) relative to an intravenous (IV) control. The availability of hGH decreased to approximately 30–40% when either peripheral or central lymph was collected indicating that a proportion of the dose was transported via the lymph. The fraction of the administered dose collected in peripheral lymph was 61.7 ± 8.5% (mean ± SEM), whereas only 8.6 ± 1.3% was collected in central lymph. These results suggested that loss of hGH within the lymphatics contributed significantly to its reduced systemic availability following SC administration. The total recovery (sum of the systemic availability and the cumulative amount recovered in lymph) of hGH was approximately 93% of the dose in the peripherally-cannulated group indicating that loss at the injection site was minimal. © 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 168–177, 2000

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