Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection
| Autor: | Laurence J. Hirsch, Ronald J. Pettis, Elaine McVey, Barry H. Ginsberg, Diane E. Sutter, Lutz Heinemann, Leszek Nosek, Steven Keith, Noel G. Harvey, Marcus Hompesch, Christoph Kapitza |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Injections Intradermal Endocrinology Diabetes and Metabolism medicine.medical_treatment Glucose uptake Injections Subcutaneous Biological Availability Absorption Subcutaneous injection Young Adult Endocrinology Pharmacokinetics Internal medicine medicine Insulin lispro Humans Hypoglycemic Agents Insulin Cross-Over Studies Insulin Lispro business.industry Glucose clamp technique Middle Aged Crossover study Medical Laboratory Technology Diabetes Mellitus Type 1 Pharmacodynamics Area Under Curve Glucose Clamp Technique business medicine.drug |
| Zdroj: | Diabetes technologytherapeutics. 13(4) |
| ISSN: | 1557-8593 |
| Popis: | This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions.Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5).Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites.Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted. |
| Databáze: | OpenAIRE |
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