Insulin Detemir Half-Life
The terminal half-life of insulin detemir (Levemir) is 5 to 7 hours depending on dose after subcutaneous administration. 1
Pharmacokinetic Profile
The FDA-approved prescribing information clearly states that insulin detemir has a terminal half-life of 5-7 hours following subcutaneous injection, with the variation dependent on the dose administered 1. This relatively short half-life is somewhat counterintuitive given detemir's classification as a long-acting insulin, but the prolonged duration of action (up to 23.2 hours at higher doses) is achieved through a different mechanism than simple half-life extension 1.
Mechanism of Prolonged Action Despite Short Half-Life
The key distinction is that detemir's duration of action is not primarily determined by its elimination half-life, but rather by its unique absorption and distribution characteristics:
- More than 98% of insulin detemir in the bloodstream is bound to albumin, which creates a depot effect and slows distribution to peripheral tissues 1
- The drug exhibits slow systemic absorption from the injection site due to strong self-association of drug molecules and albumin binding 1
- This albumin binding mechanism provides a more prolonged and consistent metabolic effect lasting 5.7 to 23.2 hours depending on dose, despite the relatively short 5-7 hour elimination half-life 1
Clinical Implications
The small apparent volume of distribution (approximately 0.1 L/kg) combined with extensive albumin binding means that while the drug is eliminated relatively quickly once it reaches systemic circulation, the rate-limiting step is the slow release from subcutaneous tissue and albumin 1. This creates a flatter, more predictable action profile compared to NPH insulin 2, 3.
Maximum serum concentrations are reached between 6 and 8 hours after administration, with absolute bioavailability of approximately 60% 1. The mean duration of action ranges from 5.7 hours at the lowest doses to 23.2 hours at the highest doses, with more than 50% of maximum effect occurring from 3-4 hours up to approximately 14 hours after administration for doses in the 0.2 to 0.4 U/kg range 1.
Special Population Considerations
- Elderly patients (≥68 years): Higher insulin AUC levels (up to 35%) due to reduced clearance, though the half-life itself remains 5-7 hours 1
- Pediatric patients: Children (6-12 years) show 10% higher AUC and 24% higher Cmax compared to adolescents and adults, but no difference in half-life is reported 1
- Renal impairment: Not specifically addressed in the FDA label for detemir's half-life, as insulin is primarily metabolized rather than renally eliminated 1