Normal fasting subjects received regular insulin and mixtures of regular with NPH or lente to assess the effects of the combinations on serum insulin concentrations (SIC) and blood glucose responses (BGR). In addition, the influence of concentration, depth, and method and site of administration was investigated. In studies of mixtures of regular with NPH and with lente, it was observed that the regular: lente ratio needed to achieve peak SIC was higher than with the regular: NPH combination. Increased SIC, including either the peak and/or the time interval required to achieve the peak, were related to the depth and site (deltoid and abdominal greater than anterior thigh or buttocks). Assuming linear kinetics of absorption, significant quantities of insulin fail to reach the serum. Marked intra- and intersubject variations in SIC and BGR to regular, NPH, and lente insulins were observed.

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Normal fasting subjects were used to study the pharmacokinetics of human insulin (recombinant DNA). Purified pork insulin (PPI) was used as a control agent. There was no difference in serum concentrations between neutral regular human insulin and PPI after intravenous administration. When given subcutaneously, peak concentrations are occasionally higher for human insulin than for PPI. The bioavailability indices for the two insulins are essentially the same. NPH human insulin produced a slightly higher serum concentration after 4 h than did NPH PPI. Studies with 70/30 NPH-regular mixtures suggest that the affinity of protamine for human insulin is less than that for PPI. The serum insulin concentrations after lente human insulin and PPI were not different. These studies, and a review of the published clinical pharmacologic literature, indicate that when present the differences between human insulin and PPI are minimal.