Pharmacokinetics of glucagon after intravenous, intraperitoneal and subcutaneous administration in a pig model

INTRODUCTION: There is increasing scientific evidence to substantiate using low‐dose glucagon as a supplement to insulin therapy in artificial pancreata for diabetes mellitus type 1. The delivery of both these hormones intraperitoneally would mimic normal physiology. However, our knowledge of the pharmacological properties of glucagon after intraperitoneal administration is limited. This study compared the pharmacokinetics of glucagon after intraperitoneal, subcutaneous and intravenous administration and the pharmacodynamic effects of glucagon on glucose metabolism after intraperitoneal and subcutaneous administration in a pig model. MATERIALS AND METHODS: Twelve pigs were included. Glucagon was administered intraperitoneally, subcutaneously and intravenously in a randomised order. Arterial samples were collected every 2–10 min for 150 min to determine plasma glucagon and blood glucose concentrations. RESULTS: The bioavailability of glucagon was significantly lower after intraperitoneal compared with subcutaneous administration with a median difference (95% confidence interval) of 13% (4–22). The effect of glucagon on glucose metabolism was equal after intraperitoneal and subcutaneous administration. CONCLUSIONS: Intraperitoneal glucagon administration resulted in lower systemic glucagon exposure than subcutaneous administration without loss of efficiency. We interpret this as evidence of a major first‐pass metabolism of glucagon in the liver.