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Short Reports

Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin

  1. Edith W Ter Braak, MD,
  2. James R Woodworth, PHD,
  3. Rutgert Bianchi, MD,
  4. Benito Cerimele, PHD,
  5. D Willem Erkelens, MD, PHD,
  6. Jos H H Thijssen, PHD and
  7. Darcie Kurtz, MS
  1. Lilly Laboratory for Clinical Research, Eli Lilly and Company, Wishard Memorial Hospital Indianapolis, Indiana
  2. Department of Internal Medicine, Utrecht University Hospital Utrecht, The Netherlands
  1. Address correspondence and reprint requests to James R. Woodworth, PhD, Lilly Laboratory for Clinical Research, Eli Lilly and Company, Wishard Memorial Hospital, 1001 W. 10th St., Indianapolis, IN 46219. E-mail: woody{at}lilly.com.
Diabetes Care 1996 Dec; 19(12): 1437-1440. https://doi.org/10.2337/diacare.19.12.1437
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Abstract

OBJECTIVE The pharmacokinetics and glucodynamics of a new insulin analog, insulin lispro, and regular human insulin were compared and contrasted after subcutaneous administrations in femoral, deltoid, and abdominal injection sites.

RESEARCH DESIGN AND METHODS Single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 healthy subjects in a six-way randomized crossover fashion. Each dose was given after an overnight fast in one of three injection sites: abdominal, deltoid, or femoral. Study drugs were given during a manual euglycemic glucose clamp. Blood samples were collected over the 12-h clamp for measurement of insulin-reactive components, with pharmacokinetic and glucodynamic measurements derived from these serum insulin and clamp measurements.

RESULTS Glucodynamic comparisons between insulin lispro and regular insulin showed a greater maximum infusion rate (Rmax) at an earlier time (TRmax), regardless of injection site. The total glucose infused (Gtot) showed nearly identical values between sites for insulin lispro. Regular insulin showed greater Gtot values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater Gtot, primarily driven by the increased Gtot from deltoid and femoral injections. Greater maximum serum insulin concentrations (Cmax) were experienced with insulin lispro at earlier times (tmax), regardless of the injection site (P < 0.001). Abdominal administrations produced the greatest Cmax values at the earliest tmax for both regular insulin and insulin lispro. Deltoid and femoral injections had lower Cmax values for both compounds. Shifts also occurred with tmax, although these shifts were much greater with regular insulin than with insulin lispro. Equivalent area under the curve (AUC) values were found when compared between compounds.

CONCLUSIONS Slower absorption from deltoid and femoral administrations resulted in an increased duration of action for both regular insulin and insulin lispro when compared to abdominal administration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro response from abdominal and extremity injection sites allows more potential sites for subcutaneous injection with an assured rapid response.

  • Received February 14, 1996.
  • Revision received August 1, 1996.
  • Accepted August 1, 1996.
  • Copyright © 1996 by the American Diabetes Association

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December 1996, 19(12)
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Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin
Edith W Ter Braak, James R Woodworth, Rutgert Bianchi, Benito Cerimele, D Willem Erkelens, Jos H H Thijssen, Darcie Kurtz
Diabetes Care Dec 1996, 19 (12) 1437-1440; DOI: 10.2337/diacare.19.12.1437

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Injection Site Effects on the Pharmacokinetics and Glucodynamics of Insulin Lispro and Regular Insulin
Edith W Ter Braak, James R Woodworth, Rutgert Bianchi, Benito Cerimele, D Willem Erkelens, Jos H H Thijssen, Darcie Kurtz
Diabetes Care Dec 1996, 19 (12) 1437-1440; DOI: 10.2337/diacare.19.12.1437
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