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Modeling absorption kinetics of subcutaneous injected soluble insulin
E Mosekilde1, K S Jensen, C Binder
1Physics Laboratory III, Technical University of Denmark, Lyngby.
Journal of Pharmacokinetics and Biopharmaceutics
|February 1, 1989
Summary
This study models subcutaneous insulin absorption, revealing it depends on injection volume and concentration. A new model accurately predicts insulin levels, optimizing delivery for stable blood glucose control.
Area of Science:
- Pharmacokinetics and Drug Delivery
- Biomedical Engineering
- Endocrinology
Background:
- Subcutaneous insulin absorption kinetics are complex, deviating from simple models.
- Insulin exists in multiple forms (low molecular weight, high molecular weight, bound) in subcutaneous tissue.
- Absorption rate is influenced by injection volume and concentration.
Purpose of the Study:
- To develop a predictive model for subcutaneous insulin absorption.
- To elucidate the roles of insulin molecular forms and binding in absorption.
- To optimize insulin delivery schedules for stable plasma insulin concentrations.
Main Methods:
- Developed a kinetic model incorporating insulin diffusion, binding, and interconversion.
- Determined key kinetic parameters (diffusion constant, absorption rate, equilibrium, binding capacity, bound state lifetime).
- Simulated plasma free insulin concentrations using bolus injection and pump delivery models.
Main Results:
- The model accurately accounts for absorption variations with volume and concentration.
- Identified significant binding of insulin at low concentrations in subcutaneous tissue.
- Simulations indicate 1-2 hour pump repetition frequency ensures near-constant plasma insulin levels.
Conclusions:
- The developed model provides a robust framework for understanding subcutaneous insulin absorption.
- Insulin binding and molecular form dynamics are critical for absorption kinetics.
- Optimized insulin pump parameters can achieve stable glycemic control in type 1 diabetes.