Comparative clinical pharmacology of human insulin (Novo) and porcine insulin in normal subjects.

The pharmacokinetics and pharmacologic effects of human insulin (Novo) derived from porcine insulin were studied by a double-blind crossover comparison with porcine monocomponent insulin in healthy volunteers. Both insulins were given by subcutaneous (s.c.) and intravenous (i.v.) injection to healthy male volunteers. The doses of injected insulin were 0.05 U/kg and 0.1 U/kg for the s.c. study, and 0.025 U/kg and 0.05 U/kg for the i.v. study. The plasma immunoreactive insulin (IRI) increased rapidly, plasma C-peptide and glucose decreased gradually, and plasma glucagon increased transiently after injection of the insulins. The pharmacokinetics and pharmacologic actions of human insulin were essentially similar to those of porcine insulin. The area under the time-concentration curve (AUC) of IRI was slightly greater after s.c. injection of human insulin than after that of porcine insulin at the 0.05-U/kg dose level. Because no significant difference was observed in the plasma C-peptide level and no such difference was noticed in the AUC of IRI between the two insulins after i.v. injection, the bioavailability of human insulin seemed to be greater than that of porcine insulin after s.c. injection. The plasma glucose-reducing effect was slightly greater after s.c. injection of 0.05 U/kg of human insulin than after s.c. injection of the same dose of porcine insulin. Apart from symptoms of hypoglycemia (sweating, palpitations, and hot flushes), no other unwanted reactions were observed after administration of either insulin. These results suggest that human insulin has a usefulness similar to that of porcine insulin in clinical practice. The clinical relevance of the slight difference in bioavailability observed in the s.c. study remains to be investigated.