SAT-171 Effective Intrajejunal Wall Delivery of Recombinant Human Insulin via a Self-Deployed Ingestible Capsule in Anesthetized Swines: A Pharmacokinetic and Pharmacodynamic Study
| Autor: | Radhika Korupolu, Mir A. Imran, Padma Karamchedu, Baber Syed, Kyle Horlen, Simret Beraki, Arvinder K. Dhalla, Mir Hashim, Rodolphe Ruffy |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
business.industry
Endocrinology Diabetes and Metabolism Capsule Pharmacology Diabetes Mellitus and Glucose Metabolism law.invention Novel Aspects of Diabetes and Metabolic Disease Across Tissues and Developmental Stages Pharmacodynamic Study Pharmacokinetics law Recombinant DNA Human insulin Medicine business |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | BACKGROUND: Biotherapeutic agents must be administered parenterally to reach and maintain therapeutic blood concentrations, lowering patient compliance and complicating long-term care. We have developed an ingestible robotic pill capable of delivering a variety of drugs directly into the wall of the proximal small intestine. METHODS: This observational, pilot study was performed in 17 juvenile anesthetized pigs under a 60-80 mg/dl euglycemic glucose clamp. All animals underwent midline, abdominal laparotomies. In a TEST group of 8 pigs (mean weight = 17.4±1.2 kg), 20 IU of recombinant human insulin (RHI) were auto-injected into the jejunal wall by inserting the pill into the proximal jejunum via a 1-cm enterotomy. A CONTROL group of 9 pigs (17.0±0.4 kg) received 20 IU of RHI injected subcutaneously. In both study groups, blood samples were collected at 10-min intervals, between -20 and +420 min after RHI administration for measurements of blood concentrations of glucose, using a handheld glucometer, and serum insulin, using the ELISA method. RESULTS: The peak serum concentrations (Cmax) of RHI were 517±109 and 342±50 pM for the jejunal wall and the subcutaneous groups, respectively (ns). The area under the insulin concentration curves (83±18 and 81±10 nmol/l.min) were likewise similar in both groups. The mean time to peak serum concentration of insulin (Tmax) was 139±42 min in the jejunal wall group, shorter than in the subcutaneous group (227±24 min). CONCLUSIONS: 1) The bioactivity of RHI was preserved after its delivery into the jejunal wall, 2) the jejunal wall route provided a more rapid and physiologic uptake of insulin compared with the subcutaneous route, though the difference (p=0.097) was not statistically significant, and 3) the pharmacokinetic and pharmacodynamic profile of RHI after its jejunal wall delivery suggests that drugs such as basal insulin, currently administered parenterally, could be successfully delivered into the proximal intestinal wall via the ingestible robotic capsule. |
| Databáze: | OpenAIRE |
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