Thoracic Lymph Duct Catheterization with a Venous Shunt in the Nonhuman Primate

Background: Biologic therapeutics constitute up to 30% of all drugs approved from 2010 to 2018 and represent a continuous growing market. In contrast to small molecules, biologic therapeutics (>1 kDa MW) are administered parenterally or intravenously due to poor bioavailability when administered orally. The absorption and disposition of biologics that are administered subcutaneously may be absorbed via lymphatic or blood capillaries. Methods: To understand the absorption and distribution of biotherapeutics via the lymphatic system a surgical model was developed in the cynomolgus macaque (Macaca fascicularis) to allow for frequent and chronic collection of lymph fluid. Additionally, the model allowed for the recirculation of the lymph fluid into the blood stream providing true physiologic redistribution of the biologic drug from the bloodstream back into the lymph. Results: To our knowledge, models of lymphatic duct catheterization with recirculation in the NHP have not been reported. The model consisted of two surgically implanted catheters, one in the thoracic lymph duct and one in the azygous vein. These two catheters were then exteriorized and connected to each other to allow for recirculation of lymph back into the venous blood stream. The exteriorized catheters were protected within the pocket of a jacket. Thirty-one surgical procedures were performed with an overall success rate of 70%. Unsuccessful attempts were related to anatomical differences where the lymphatic duct was either not identifiable (n = 3) or too small to catheterize (n = 6). The patency rate was 90% instrumented animals for at least 24 h, up to 168 h. Conclusion: We present the surgical technique, complications, and refinements which resulted in a reliable and reproducible model in the nonhuman primate for the chronic collection and recirculation of lymphatic fluid.