Pharmacokinetics of insulin disappearance after massive overdosing

Abstract

Long-term glucose supplementation is required to prevent hypoglycemia after massive insulin overdosing. We fitted the blood insulin concentration-time profile to the model: I = A·exp + B·exp, where I (μU/mL) is the serum/plasma insulin concentration, A (μU/mL) and B (μU/mL) are the peak insulin concentrations of each component, a (time) and b (time) are the time constants of each component, and t (h) is the time elapsed from the peak of blood insulin level. Additional components were considered as needed. Patient 1 had auto-injected 600 U NovoRapid 30Mix, and Patient 2 had auto-injected 300 U NovoletR (regular) and 1,800 U NovoLetN (NPH). We used the disappearance of therapeutic doses of the respective insulin in healthy individuals as controls, and we obtained parameters by Excel solver. In Patient 1, the parameter values were A = 1490.04 and a = 0.15 for insulin aspart and B = 60.66 and b = 0.04 for protaminated aspart. In Patient 2, the values were A = 784.45 and a = 0.38 for regular insulin and B = 395.84 and b = 0.03 for NPH. Compared with controls, the half-lives (t) for insulin aspart and protaminated aspart were 4 and 2 times longer, respectively, in Patient 1. In Patient 2, the t for regular and NPH insulin were 2 and 7 times longer than those in the controls, respectively. In conclusion, the t for insulin was elongated 2 to 7 times after massive overdosing, explaining why glucose supplementation is needed for long periods in these cases.

Be aware of critical drugs in emergency departments: An extreme iatrogenic insulin overdose via subcutaneous and intramuscular routes

“…The peak effect starts approximately at 2.5 hours and terminates in 5-8 hours after the incident. However, the half-life of insulin is elongated after massive overdosing, necessitating more prolonged close monitoring of glucose levels 11 . Our patient stayed in ICU for two days in total.…”