Pharmacokinetic and Pharmacodynamic Variability of Insulin When Administered by Jet Injection.

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.

Needle-free jet injection of rapid-acting insulin improves early postprandial glucose control in patients with diabetes.

OBJECTIVE: Clamp studies have shown that the absorption and action of rapid-acting insulin are faster with injection by a jet injector than with administration by conventional pen. To determine whether these pharmacokinetic changes also exist in patients with diabetes and benefit postprandial glucose control, we compared the pharmacologic profiles of insulin administration by jet injection versus conventional insulin pen after a standardized meal in patients with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and 12 patients with type 2 diabetes received insulin aspart either by jet injection or by conventional pen, in both cases followed by a standardized meal. Blood was sampled for 6 h for determination of glucose and insulin levels to calculate pharmacologic profiles. RESULTS: Insulin administration by jet injection resulted in shorter time until peak plasma insulin level (51.3 ± 6.4 vs. 91.9 ± 10.2 min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 ± 20.8 vs. 196.3 ± 18.4 mmol · min · L(-1); P = 0.041) compared with conventional administration. Jet injection did not, however, significantly reduce the hyperglycemic burden during the 5-h period thereafter. There was no indication that the jet injector performed differently in patients with type 1 and type 2 diabetes. CONCLUSIONS: The considerably more rapid insulin absorption after administration by jet injector translated to a significant if modest decrease in postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The improved early postprandial glucose control may specifically benefit patients who have difficulty in limiting postprandial glucose excursions.

Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology.

OBJECTIVE: Insulin administered by jet injectors is dispensed over a larger subcutaneous area than insulin injected with a syringe, which may facilitate a more rapid absorption. This study compared the pharmacologic profile of administration of insulin aspart by jet injection to that by conventional insulin pen. RESEARCH DESIGN AND METHODS: Euglycemic glucose clamp tests were performed in 18 healthy volunteers after subcutaneous administration of 0.2 units/kg body wt of aspart, either administered by jet injection or by conventional pen, using a randomized, double-blind, double-dummy, cross over study design. Pharmacodynamic and pharmacokinetic profiles were derived from the glucose infusion rate (GIR) needed to maintain euglycemia and from plasma insulin levels, respectively. RESULTS: The time to maximal GIR was significantly shorter when insulin was injected with the jet injector compared with conventional pen administration (51 ± 3 vs. 105 ± 11 min, P < 0.0001). The time to peak insulin concentration was similarly reduced (31 ± 3 vs. 64 ± 6 min, P < 0.0001) and peak insulin concentrations were increased (108 ± 13 vs. 79 ± 7 mU/L, P = 0.01) when insulin was injected by jet injection compared with conventional pen injection. Jet injector insulin administration reduced the time to 50% glucose disposal by ∼40 min (P < 0.0001). There were no differences in maximal GIR, total insulin absorption, or total insulin action between the two devices. CONCLUSIONS: Administration of insulin aspart by jet injection enhances insulin absorption and reduces the duration of glucose-lowering action. This profile resembles more closely the pattern of endogenous insulin secretion and may help to achieve better meal insulin coverage and correction of postprandial glucose excursions.