Comparative pharmacokinetics and glucodynamics of two human insulin mixtures. 70/30 and 50/50 insulin mixtures.

OBJECTIVE To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg. RESEARCH DESIGN AND METHODS We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and Cpeptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (C max ), time to maximum insulin concentration ( t max ), terminal rate constant (β), area under the curve from 0 to ∞, (AUC x 0 ), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [C min ], time to minimum C-peptide concentration [ t min ], area between the C-peptide baseline and the C-peptide suppression curve [AOC c ], absolute maximal difference from baseline [S diff ] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (R max ) and time to R max (TR max ) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h ( 4 0 G tot ) and total glucose infused (G tot ) during the study. RESULTS For the pharmacokinetic assessment, statistically greater values of insulin C max and β were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of R max and ( 4 0 G tot ) found with the 50/50 mixture. Notably, differences were not detected for insulin AUC x 0 and G tot values. CONCLUSIONS Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.