What is the half-life of NPH (Neutral Protamine Hagedorn) insulin?

Half-Life of NPH Insulin

NPH (Neutral Protamine Hagedorn) insulin has a half-life of approximately 6.6 hours, with its peak effect occurring around 8-12 hours after injection and a total duration of action of about 18-24 hours. 1, 2

Pharmacokinetic Profile of NPH Insulin

• NPH insulin begins to lower blood glucose approximately 1-2 hours after subcutaneous injection 1
• Peak effect occurs at approximately 8-12 hours after injection 3, 1
• Total duration of action is approximately 18-24 hours, with studies showing a range of 20-29 hours 1
• The half-life of NPH insulin in subcutaneous tissue has been measured at 6.6 ± 3.3 hours 2

Clinical Implications of NPH Pharmacokinetics

Advantages

• Intermediate-acting profile makes it suitable for basal insulin coverage
• Can be administered once or twice daily depending on patient needs
• Can be mixed with short-acting or rapid-acting insulins for combined coverage 3, 4

Disadvantages

• The pronounced peak at 8-12 hours increases risk of hypoglycemia, particularly when administered at bedtime 3
• More variable absorption compared to newer basal insulin analogs
• In elderly patients, NPH has been associated with higher rates of hypoglycemia compared to basal-bolus regimens with insulin analogs 3, 4

Practical Applications

Dosing Considerations

• When used as basal insulin, NPH is typically administered as:
  • Once daily: Usually in the morning or at bedtime
  • Twice daily: Typically 2/3 in the morning and 1/3 in the evening 4
• Initial dosing can start at 0.1-0.2 units/kg per day with titration based on glucose patterns 4

Mixing Guidelines

• NPH can be mixed with rapid-acting or short-acting insulins 3, 4
• When mixed with rapid-acting insulin, the mixture should be injected within 15 minutes before a meal 3, 4
• NPH should NOT be mixed with lente insulins due to potential precipitation of zinc phosphate 3, 4
• Currently available NPH and short-acting insulin formulations when mixed may be used immediately or stored for future use 3

Important Considerations

• The pronounced peak of NPH insulin at 8-12 hours can lead to nocturnal hypoglycemia when administered at bedtime 3, 5
• Newer long-acting insulin analogs (like insulin glargine) offer a smoother time-action profile with less pronounced peaks compared to NPH 5, 6
• Storage conditions affect potency: NPH insulin should be stored according to manufacturer guidelines, typically refrigerated when not in use 3
• Visual inspection before use is important: NPH insulin should appear uniformly cloudy; any clumping, frosting, precipitation, or change in clarity may indicate loss of potency 3

Clinical Pitfalls to Avoid

• Assuming NPH has a consistent effect throughout its duration of action (it has a pronounced peak)
• Failing to account for the peak action when timing doses relative to meals and sleep
• Overlooking the increased hypoglycemia risk in elderly patients using NPH compared to newer insulin analogs 3, 4
• Inappropriate mixing with other insulin types (particularly lente insulins) 3, 4