Absorption kinetics of insulin after subcutaneous administration

Søeborg, Tue; Rasmussen, Christian Lund; Mosekilde, Erik; Colding‐Jørgensen, Morten

doi:10.1016/j.ejps.2008.10.018

Cited by 93 publications

(90 citation statements)

References 68 publications

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“…Approximately 98% of detemir within the blood stream is bound to albumin [2,5]. In contrast the prolongation of action of NPH insulin in the subcutaneous depot is dependent on non-covalent associations with zinc atoms and with protamine, such that after absorption into the circulation it exists in the free form identical to native human insulin [6].…”

Section: Introductionmentioning

confidence: 99%

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

et al. 2009

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Aims/hypothesis We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(ε-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake. Methods After overnight intravenous infusion of soluble human insulin 18 participants with type 1 diabetes received subcutaneous injections of NPH insulin or insulin detemir (0.5 U/kg body weight) on separate occasions in random order. During the ensuing gradual development of hypoglycaemia cognitive function and levels of counter-regulatory hormones were measured and rates of endogenous glucose production and peripheral glucose uptake continuously evaluated using a primed constant infusion of [6,6-2 H 2 ] glucose. The study was terminated when plasma glucose concentration had fallen to 2.4 mmol/l or had reached a minimum at a higher concentration. Results During the development of hypoglycaemia no difference between the two insulin preparations was observed in symptoms or hormonal responses. Significant differences were seen in rates of glucose flux. At and below plasma glucose concentrations of 3.5 mmol/l suppression of endogenous glucose production was greater with insulin detemir than with NPH insulin, whereas stimulation of peripheral glucose uptake was greater with NPH insulin than with insulin detemir. Conclusions/interpretation In participants with type 1 diabetes subcutaneously injected insulin detemir exhibits relative hepatoselectivity compared with NPH insulin, but symptoms of hypoglycaemia and hormonal counterregulation are similar.

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Section: Introductionmentioning

confidence: 99%

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

et al. 2009

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“…Reprinted with permission from Søeborg and colleagues. 48 that favor hexamer dissociation, which ultimately increases the rate of insulin absorption. 10,23 Thus, administration of rHuPH20 has the potential to reduce concentrationand dose-mediated limitations imposed on standard insulin formulations.…”

Section: Clinical Pharmacology Studiesmentioning

confidence: 99%

Section: Mechanisms Underlying Absorption Kinetics Of Subcutaneously mentioning

confidence: 99%

“…48 Insulin hexamers are too large to be absorbed across capillary walls and must dissociate into dimers or monomers before absorption can occur. 48,49 Spontaneous dissociation of insulin occurs at low concentrations via equilibrium shift. In a traditional subcutaneous injection, insulin absorption is diffusion limited; insulin hexamers must first diffuse away from the site of injection to dissociate and become available for absorption.…”

Section: Mechanisms Underlying Absorption Kinetics Of Subcutaneously mentioning

confidence: 99%

“…41 Thus, the absorption of insulin is affected by both insulin concentration and dose (Figure 2). 48 High concentrations and high doses are absorbed more slowly because of diffusion limitations.…”

Section: Mechanisms Underlying Absorption Kinetics Of Subcutaneously mentioning

confidence: 99%

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Review of the Mechanism of Action and Clinical Efficacy of Recombinant Human Hyaluronidase Coadministration with Current Prandial Insulin Formulations

Muchmore

Vaughn

2010

Journal of Diabetes Science and Technology

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Abbreviations: (A1C) derived average glucose, (C max ) peak plasma concentration, (PK) pharmacokinetics, (PPG) postprandial plasma glucose, (rHuPH20) recombinant human hyaluronidase, (SC) subcutaneous, (t max ) time to peak plasma concentration Keywords: diabetes, glycemic control, hyaluronidase, rHuPH20, ultrafast insulin AbstractFor patients with type 1 or type 2 diabetes, achieving good glycemic control is critical for successful treatment outcomes. As many patients remain unable to reach glycemic goals with currently available rapid-acting analog insulins, ultrafast insulin products are being developed that provide an even faster pharmacokinetic profile compared with current rapid prandial insulin products. The overall strategy of these ultrafast insulin products is to better mimic the normal physiologic response to insulin that occurs in healthy individuals to further improve glycemic control. Recombinant human hyaluronidase (rHuPH20) is a genetically engineered soluble hyaluronidase approved by the U.S. Food and Drug Administration as an adjuvant to increase the absorption and dispersion of other injected drugs; mammalian hyaluronidases as a class have over 6 decades of clinical use supporting the safety and/or efficacy of hyaluronidase coadministration. Clinical findings have demonstrated that coadministration of rHuPH20 with insulin or an insulin analog achieved faster systemic absorption, reduced inter-and intrapatient variability of insulin absorption, and achieved faster metabolic effects compared with injection of either insulin formulation alone. The magnitude of this acceleration is similar to the incrementally faster absorption of prandial insulin analogs as compared with regular insulin. In addition, coadministration of rHuPH20 with regular insulin or insulin analog also improved the achievement of prandial glycemic targets. Thus, rHuPH20 coadministration shows promise as a method of establishing a more rapid insulin profile to prandial insulin in patients with diabetes and has the potential to yield substantial improvements in postprandial glycemic excursion.

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Insulin and Insulin Treatment

Gough

Narendran

2016

Textbook of Diabetes

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Absorption kinetics of insulin after subcutaneous administration

Cited by 93 publications

References 68 publications

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

Review of the Mechanism of Action and Clinical Efficacy of Recombinant Human Hyaluronidase Coadministration with Current Prandial Insulin Formulations

Insulin and Insulin Treatment

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