Improved Pharmacokinetic and Pharmacodynamic Profile of Rapid-Acting Insulin Using Needle-Free Jet Injection Technology

Abstract

OBJECTIVEInsulin 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 METHODSEuglycemic 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.RESULTSThe 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.CONCLUSIONSAdministration 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.

Lispro administered by the QS-M Needle-Free Jet Injector generates an earlier insulin exposure

“…Some studies have reported no local reactions after jet injections of insulin [3], whereas others have reported significant reaction, including immediate pain, delayed pain, bleeding, and hematomas [6,7]. In the present study, a trained nurse was arranged to perform the injection, and no hematomas, bruising, and bleeding were reported in the needle-free injection group.…”

“…A non-randomized study has evaluated profiles of insulin lispro using jet injector technology, but the sample size was small and the dose of insulin lispro was unreasonable [5]. A study conducted by Engwerda et al in 18 healthy volunteers, using a randomized, double-blind, double-dummy, crossover study design, found that GIR-Tmax as well as INS-Tmax were significantly shorter when aspart was injected by jet injection compared to conventional pen injection [3]. The results of our experiment were consistent with the above studies and further confirmed the advantage of the QS-M jet injector for delivering lispro in the Chinese population.…”

“…Rapid-acting insulin analogs more closely approach the physiological insulin response, compared with regular human insulin [2]. Nevertheless, rapid-acting insulin analogs administered by conventional pen could not be absorbed quickly enough to replicate the physiological insulin secretion profile [3].…”

“…Previous studies revealed that insulin administered by jet injectors is absorbed faster compared to conventional insulin pens [5][6][7][8][9]. A randomized, double-blind, double-dummy, crossover study conducted by Engwerda et al [3] showed that compared to the conventional pen, enhanced insulin absorption and reduced duration of glucose-lowering action were found when aspart was administered by the jet injector. Whether the differences in the pharmacokinetic and pharmacodynamic (PK-PD) profiles can be extrapolated to other rapid-acting insulin analogs needs to be further investigated.…”

Dynamic behavior of a spring-powered micronozzle needle-free injector

“…The latter limits intra-and inter-individual reproducibility of the key pharmacokinetics parameters with obvious issues on formulation bioequivalence. This inconsistency seems to be device related because some of them have shown even better pharmacokinetic and pharmacodynamic parameters than conventional injection (Engwerda et al, 2011;Engwerda et al, 2013).…”