Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Naruto, Japan.
Xenotransplantation. 2019 Jul;26(4):e12505. doi: 10.1111/xen.12505. Epub 2019 Feb 28.
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.
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 (t ) and area under the time-concentration curve (AUC ).
After intraperitoneal C-peptide injection, the highest porcine C-peptide concentration in peripheral blood was only one-fortieth compared to after intravenous injection. The AUC 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.
Porcine C-peptide injected into a peritoneal cavity slowly and incompletely entered peripheral circulation, which resulted in very low concentration in peripheral blood.
此前，我们已经证明，在糖尿病裸鼠的腹腔内移植包被胰岛时，C-肽浓度非常低，血糖水平正常。此外，腹腔内腹水的 C-肽浓度比外周血高 40 倍。在这项研究中，我们研究了腹腔内猪 C-肽的药代动力学。
为了评估猪 C-肽的药代动力学，通过尾静脉或低剂量（200pmol/kg）或高剂量（2000pmol/kg）分别将合成的猪 C-肽溶液注入腹腔，在大鼠的外周循环中或腹腔内注入。注射后 1-120 分钟内每隔一段时间采集动脉血样，以计算末端消除半衰期（t ）和时间-浓度曲线下面积（AUC）。
腹腔内 C-肽注射后，外周血中猪 C-肽的最高浓度仅为静脉注射后的四十分之一。低剂量时腹腔注射的 AUC 为静脉注射的 78%，高剂量时仅为 39%。这一发现表明，当腹腔内移植的胰岛通过高葡萄糖刺激释放 C-肽时，C-肽仍留在腹腔内。
注入腹腔的猪 C-肽缓慢且不完全进入外周循环，导致外周血中浓度非常低。
