A stepwise surgical procedure to investigate the lymphatic transport of lipid-based oral drug formulations: Cannulation of the mesenteric and thoracic lymph ducts within the rat

Abstract

Introduction: A number of animal models have been described for the assessment of intestinal lymphatic drug transport. Lymphatic transport studies are commonly first conducted in the laboratory rat, with larger more complicated models (i.e., dog or pig) subsequently investigated. However, the utility of lymph fistulation in large animals is limited by considerable logistical and economic constraints. Methods: This paper describes a stepwise surgical procedure for cannulating the thoracic and mesenteric lymph ducts in male Sprague–Dawley rats. Results: Following surgery, thoracic and mesenteric lymph flow rates during the 24-h period immediately following surgery averaged 12.5±2.5 and 2.4±1.1 ml/h, respectively. This flow rate is greater than that obtained with previously described methods, which require restraint of the animals and/or a 24-h recovery period and are reported to produce average intestinal lymph flow rates of 2 ml/h. Discussion: This animal model can be utilized for the assessment of drug transport by the lymphatics and for determining what percentage of lymphatic transport is a result of only intestinal lymphatics.