Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats

Absorption kinetics of regular, isophane (NPH), and protamine zinc (PZI) insulin were evaluated in seven clinically normal domestic shorthair cats by measurement of serial serum concentrations of insulin after subcutaneous administration of each insulin preparation. These results were compared to measurements of serial serum insulin concentrations after similar dosages of regular insulin were administered intravenously. Regular insulin administered subcutaneously was better absorbed than NPH and PZI insulins (mean bioavailability index 45.4% vs. 33.0% for NPH and 27.3% for PZI), and resulted in a significantly greater maximal increase in mean circulating insulin concentrations above baseline values (3529 pM vs. 1044 pM for NPH and 344 pM for PZI, P less than 0.05). The mean time interval between insulin administration and time to reach peak concentrations was significantly shorter for regular insulin than for NPH or PZI insulin (0.5 hr vs. 1.6 hr for NPH and 4.1 hr for PZI, P less than 0.05). There was also a significant difference (P less than 0.05) in the mean time interval between insulin injection and return of serum insulin concentrations to baseline values between regular insulin (5.6 hr) and NPH (7.7 hr) or PZI (13.1 hr) insulins. When compared with PZI, NPH insulin showed a significantly (P less than 0.05) greater maximal increase in mean serum insulin concentrations over baseline values. In addition, the interval between insulin administration and time to reach peak concentrations, as well as the time between insulin injection and return of serum insulin concentrations to baseline values, were also significantly shorter with NPH insulin than with PZI. These results suggest that NPH and PZI insulins administered subcutaneously to cats may require a short time to reach peak serum insulin concentrations as well as a relatively short time for circulating insulin concentrations to return to baseline values. If the absorption kinetics are similar to that in this study, most cats with diabetes mellitus would need twice daily injection of NPH or PZI insulin to adequately control the diabetic state.