Clinical pharmacologic studies with human insulin (recombinant DNA)

Area of Science:

• Pharmacology
• Endocrinology
• Biochemistry

Background:

• Understanding the pharmacokinetic profiles of different insulin formulations is crucial for effective diabetes management.
• Human insulin produced via recombinant DNA technology is a key therapeutic agent, necessitating comparison with older insulin sources like purified pork insulin (PPI).

Purpose of the Study:

• To compare the pharmacokinetics of neutral regular human insulin and purified pork insulin (PPI) in normal fasting subjects.
• To evaluate the bioavailability and serum concentrations of various human insulin formulations (NPH, lente, and mixtures) against their PPI counterparts.

Main Methods:

• Intravenous and subcutaneous administration of human insulin and PPI in normal fasting subjects.
• Measurement of serum insulin concentrations over time.
• Calculation of bioavailability indices.
• Assessment of NPH-human insulin and NPH-PPI, including 70/30 NPH-regular mixtures.

Main Results:

• No significant difference in serum concentrations between neutral regular human insulin and PPI after intravenous administration.
• Subcutaneous administration showed occasionally higher peak concentrations for human insulin compared to PPI, with similar bioavailability indices.
• NPH human insulin demonstrated slightly higher serum concentrations after 4 hours than NPH PPI; protamine affinity was lower for human insulin.

Conclusions:

• Pharmacokinetic differences between human insulin and purified pork insulin are minimal.
• The observed differences, particularly in NPH formulations, do not suggest significant clinical implications for diabetes treatment.
• Human insulin and PPI exhibit comparable pharmacokinetic behavior, supporting the interchangeability of these insulin types in clinical practice.