Journal Article

Pharmacokinetics and Pharmacodynamics of High-Dose Human Regular U-500 Insulin Versus Human Regular U-100 Insulin in Healthy Obese Subjects

Linnebjerg, Helle, Jacobson, Jennie G, Morrow, Linda A, Scott, Adam, Mace, Kenneth F, Jiang, Honghua H, Hompesch, Marcus, Riddle, Matthew, Jackson, Jeffrey A, de la Peña, Amparo, Win, Khin M

2011

Overview

OBJECTIVE: Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK and PD of clinically relevant doses of U-500R with the same doses of human regular U-100 (U-100R) insulin (100 units/mL). RESEARCH DESIGN AND METHODS: This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections of 50- and 100-unit doses of U-500R and U-100R were administered to 24 healthy obese subjects. RESULTS: Both overall insulin exposure (area under the serum insulin concentration versus time curve from zero to return to baseline [AUC0-t’]) and overall effect (total glucose infused during a clamp) were similar between formulations at both 50- and 100-unit doses (90% [CI] of ratios contained within [0.80, 1.25]). However, peak concentration and effect were significantly lower for U-500R at both doses (P < 0.05). Both formulations produced relatively long durations of action (18.3 to 21.5 h). Time-to-peak concentration and time to maximum effect were significantly longer for U-500R than U-100R at the 100-unit dose (P < 0.05). Time variables reflective of duration of action (late tRmax50, tRlast) were prolonged for U-500R versus U-100R at both doses (P < 0.05). CONCLUSIONS: Overall exposure to and action of U-500R insulin after subcutaneous injection were no different from those of U-100R insulin. For U-500R, peaks of concentration and action profiles were blunted and the effect after the peak was prolonged. These findings may help guide therapy with U-500R insulin for highly insulin-resistant patients with diabetes.

• Publisher: American Diabetes Association
• Subject: administered dose / administration & dosage / Adult / Aged / Area Under Curve / Biological and medical sciences / Blood Glucose / Blood Glucose - drug effects / blood serum / Clinical medicine / Cross-Over Studies / Diabetes / Diabetes. Impaired glucose tolerance / Dosage and administration / Double-Blind Method / drug effects / drug therapy / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Female / Glucose / Glucose Clamp Technique / Humans / Hypoglycemic Agents / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - pharmacokinetics / Hypoglycemic Agents - pharmacology / Insulin / Insulin resistance / Insulin, Regular, Human / Insulin, Regular, Human - administration & dosage / Insulin, Regular, Human - pharmacokinetics / Insulin, Regular, Human - pharmacology / Life sciences / Male / Medical sciences / Metabolic diseases / Middle Aged / Miscellaneous / Obesity / Obesity - drug therapy / Original Research / patients / Pharmaceutical industry / pharmacokinetics / pharmacology / Public health. Hygiene / Public health. Hygiene-occupational medicine / Statistical methods / subcutaneous injection / therapeutics