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 (–a·t) + B·exp (–b·t) , 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 –1 ) and b (time –1 ) 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 Novolet®R (regular) and 1,800 U NovoLet®N (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 1/2 ) for insulin aspart and protaminated aspart were 4 and 2 times longer, respectively, in Patient 1. In Patient 2, the t 1/2 for regular and NPH insulin were 2 and 7 times longer than those in the controls, respectively. In conclusion, the t 1/2 for insulin was elongated 2 to 7 times after massive overdosing, explaining why glucose supplementation is needed for long periods in these cases.