title: Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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, P < 0.05) 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, P < 0.05; 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: BD Technologies, Research Triangle Park, North Carolina 27709, USA. Ron_J_Pettis@bd.com
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Pettis
authors.forename: Barry
authors.initials: B
authors.lastname: Ginsberg
authors.forename: Laurence
authors.initials: L
authors.lastname: Hirsch
authors.forename: Diane
authors.initials: D
authors.lastname: Sutter
authors.forename: Steven
authors.initials: S
authors.lastname: Keith
authors.forename: Elaine
authors.initials: E
authors.lastname: McVey
authors.forename: Noel G
authors.initials: NG
authors.lastname: Harvey
authors.forename: Marcus
authors.initials: M
authors.lastname: Hompesch
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
mesh_terms: D000042:Absorption; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D061268:Insulin Lispro; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro