The pharmacokinetics of porcine C‐peptide after intraperitoneal injection

• Published in: Xenotransplantation (Københaven) 2019-07, Vol.26 (4), p.e12505-n/a
• Main Authors: Iizuka, Naho, Nishimura, Masuhiro, Fujita, Yasutaka, Sawamoto, Osamu, Matsumoto, Shinichi
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Abdominal; Area Under Curve; Ascites; Blood Glucose - analysis; Blood levels; C-Peptide - administration & dosage; C-Peptide - blood; C-Peptide - pharmacokinetics; C‐peptide; Diabetes mellitus; Glucose; Injection; Injections, Intraperitoneal; intraperitoneal transplantation; Intravenous administration; islets; Kidney - metabolism; Liver - metabolism; Male; Metabolic Clearance Rate; Peptides; Peripheral blood; Peritoneum; Pharmacokinetics; Portal Vein; Rats; Rats, Wistar; Renal Veins; Swine; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1111/xen.12505

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.