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

Degradation of human growth hormone (hGH) at the injection site has previou sly been implicated as the basis for its reduced systemic availability foll owing subcutaneous (SC) administration. The goal of these studies was to de velop an animal model which would allow mass balance calculations to (i) qu antify the loss at the injection site and (ii) determine the role of the ly mphatics in the transport of subcutaneously-administered hGH. The animal mo del utilized a sheep and enabled simultaneous sampling of blood and collect ion of either peripheral lymph (via the efferent duct of the popliteal lymp h node draining the injection site) or central lymph (via the thoracic lymp h duct). In non-lymph cannulated sheep, the systemic availability of hGH fo llowing SC dosing was 58.4 +/- 9.1% (mean +/- SEM) relative to an intraveno us (nz) control. The availability of hGH decreased to approximately 30-40% when either peripheral or central lymph was collected indicating that a pro portion of the dose was transported via the lymph. The fraction of the admi nistered 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 recov ered in lymph) of hGH was approximately 93% of the dose in the peripherally -cannulated group indicating that loss at the injection site was minimal. ( C) 2000 Wiley-Liss, Inc.