BACKGROUND: Previously, we have demonstrated that there were very low C-Peptide concentrations and normal blood glucose levels when we transplanted encapsulated islets in the abdominal cavity of diabetic nude mice. In addition, the C-peptide concentration in the ascites fluid of the peritoneal cavity was 40 times higher than in the peripheral blood. In this study, we investigated the pharmacokinetics of intraperitoneal porcine C-peptide. METHODS: To assess the pharmacokinetics of porcine C-peptide, a synthesized porcine C-peptide solution was injected into the peripheral circulation through the tail vein or into the peritoneal cavity in rats at low or high doses of either 200 or 2000 pmol/kg, respectively. Arterial blood samples were collected at time intervals of 1-120 minutes after injection to calculate the terminal elimination half-life (t1/2 ) and area under the time-concentration curve (AUC0-t ). RESULTS: After intraperitoneal C-peptide injection, the highest porcine C-peptide concentration in peripheral blood was only one-fortieth compared to after intravenous injection. The AUC0-t for the intraperitoneal injection was 78% at the low dose and only 39% at the high dose compared to the intravenous injection. This finding indicates that C-peptide remains in the abdominal cavity when intraperitoneally transplanted islets release C-peptide via high glucose stimulation. CONCLUSIONS: Porcine C-peptide injected into a peritoneal cavity slowly and incompletely entered peripheral circulation, which resulted in very low concentration in peripheral blood.
BACKGROUND: Previously, we have demonstrated that there were very low C-Peptide concentrations and normal blood glucose levels when we transplanted encapsulated islets in the abdominal cavity of diabeticnude mice. In addition, the C-peptide concentration in the ascites fluid of the peritoneal cavity was 40 times higher than in the peripheral blood. In this study, we investigated the pharmacokinetics of intraperitoneal porcine C-peptide. METHODS: To assess the pharmacokinetics of porcine C-peptide, a synthesized porcine C-peptide solution was injected into the peripheral circulation through the tail vein or into the peritoneal cavity in rats at low or high doses of either 200 or 2000 pmol/kg, respectively. Arterial blood samples were collected at time intervals of 1-120 minutes after injection to calculate the terminal elimination half-life (t1/2 ) and area under the time-concentration curve (AUC0-t ). RESULTS: After intraperitoneal C-peptide injection, the highest porcine C-peptide concentration in peripheral blood was only one-fortieth compared to after intravenous injection. The AUC0-t for the intraperitoneal injection was 78% at the low dose and only 39% at the high dose compared to the intravenous injection. This finding indicates that C-peptide remains in the abdominal cavity when intraperitoneally transplanted islets release C-peptide via high glucose stimulation. CONCLUSIONS: Porcine C-peptide injected into a peritoneal cavity slowly and incompletely entered peripheral circulation, which resulted in very low concentration in peripheral blood.