Pharmacokinetics of I-125-labeled insulin glargine (HOE 901) in healthy men - Comparison with NPH insulin and the influence of different subcutaneousinjection sites

OBJECTIVE- To determine the subcutaneous absorption rates and the appearanc e in plasma of 3 formulations of the long-acting human insulin analog insul in glargine (HOE 901) differing only in zinc content (15, 30, and 80 mu g/m l). RESEARCH DESIGN AND METHODS - We conducted 2 studies. Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of I-125-labeled insulin glar gine [15], insulin glargine[80], NPH insulin, and placebo. In study 2, 0.2 U/kg of insulin glargine[30] was injected into the arm, leg, and abdominal regions. Both studies had a randomized crossover design; each enrolled 12 h ealthy men, aged 18-50 years. RESULTS - In study 1, the time in hours for 25% of the administered radioac tivity to disappear after bolus subcutaneous injection (T-75%) for NPH insu lin indicated a significantly faster absorption rate compared with the 2 in sulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively P < 0.000 1). Mean residual radioactivity with NPH insulin was also significantly low er at 24 h (21.9 vs. 43.8 and 52.2%, P < 0.0001). The calculated plasma exo genous insulin concentrations after NPH insulin were substantially higher t han those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibi t a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P < 0.001). In study 2, there were no significant differences in the absorpt ion characteristics of insulin glargine between the 3 injection sites (T-75 % = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in r esidual radioactivity at 24 h. CONCLUSIONS - Subcutaneous absorption of insulin glargine is delayed compar ed with NPH insulin. There is little or no difference in the absorption rat e of insulin glargine between the main subcutaneous injection sites.