Pharmacokinetic and Pharmacodynamic Variability of Insulin When Administered by Jet Injection

Abstract

Background: Jet injection has been shown to accelerate the absorption and action of rapid-acting insulin. In this study, we compared the variability of absorption characteristics between jet injection and conventional administration of the rapid-acting insulin analogue aspart.

Methods: A total of 30 healthy volunteers were enrolled in this randomized controlled blinded parallel study. On two test days, they received insulin aspart (0.2 units/kg body weight), either by jet injection or conventional pen, followed by a 6-hour euglycemic glucose clamp. Plasma glucose and insulin levels and glucose infusion rates were measured every 5 to 10 minutes to calculate the variability in pharmacological endpoints.

Results: Jet injection advanced the times until maximal insulin concentration (T-INSmax) and glucose infusion rate (T-GIRmax) by ~40% (both P < .01). The difference between the two test days for these endpoints did not differ between jet injection and conventional administration (T-INSmax: 7.3 ± 1.9 vs 22.3 ± 6.3 min, P = .074; T-GIRmax: 24.0 ± 3.5 vs 27.3 ± 6.6 min, P = .66). The corresponding intraindividual coefficients of variation for injection by jet or conventional pen were 15.3 ± 3.3 and 22.0 ± 4.6% ( P = .25, Pvariance = .044) for T-INSmax and 34.5 ± 5.1 and 21.2 ± 4.6% for T-GIRmax ( P = .064, Pvariance = .62). The variance in maximal insulin concentration was significantly less after conventional administration ( P = .039). The variance in total glucose-lowering effect and total insulin exposure did not differ ( P = .93 and P = .32) Conclusion: Using a jet injector for insulin administration was associated with slightly altered variability in pharmacokinetic endpoints, but with about similar variability in pharmacodynamic endpoints compared to conventional administration. Variability in these endpoints remains considerable, regardless of the method of insulin administration.

Trial registration: ClinicalTrials.gov NCT02272296.

Keywords: diabetes mellitus; insulin aspart; jet injector; pharmacodynamics; pharmacokinetics; variability.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: European Pharma Group funded the study, but was not involved in the design or execution of the study or in the writing of the manuscript. BEdG served as a consultant for, or gave lectures organized by Novo Nordisk, Merck, and Sanofi. CJT (or his employer) has received research grants, served as a consultant for, or gave lectures organized by Merck, Janssen, AstraZeneca, and Novo Nordisk. The remaining author declares that she has no conflicts of interest.

Figures

Figure 1.

Mean plasma insulin levels (a) and glucose infusion rates (b) after insulin injection by the jet injector (solid line) and conventional pen (dashed line) on day 1 (black line) and day 2 (gray line) during the euglycemic glucose clamp.