Pharmacokinetics of long-acting (ultralente) insulin preparations

D. E. Seigler, G. M. Olsson, R. F. Agramonte, V. L. Lohman, M. H. Ashby, M. L. Reeves, J. S. Skyler

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The aim of this study was to define and characterize time course of biological action and pharmacokinetics of long-acting ultralente insulin preparations. A further aim was to compare influence of species of origin (beef, pork, human) and specific commercial formulation (Lilly, Novo) on these parameters. Five preparations were studied in 6 to 9 healthy volunteers perpreparation. Dosage was 0.4 U/kg administered subcutaneously in the abdomen. Glucose was clamped for 40 hr at basal levels. Rate of dextrose infusion required to maintain euglycemia was used as the primary means of quantifying biological effectiveness. All ultralente preparations had onset of action between 3.0 and 7.5 hr, with no statistical difference between preparations for onset of action. Likewise, there was no statistical difference between preparations for duration of action, which was greater than 30 hr for all preparations. On the other hand, Lilly human ultralente had an earlier peak of action (8.5 ± 0.9 hr) than beef ultralente, which showed only a subtle peak at a mean of 20.6 ± 3.3 hr. Novo human ultralente resulted in greater total glucose infusion than beef ultralente. Greatest reproducibility of action was with Lilly human ultralente. Curves depicting plasma insulin levels were similar in shape to dextrose infusion profiles for each preparation, thus validating the method. Compared to the total duration of insulin action seen, the peaks of action seen with the pork and human ultralente insulin preparations were quite broad and of relatively small magnitude. As a consequence of the breadth of the action peaks and the prolonged duration of action of ultralente insulin, any of the ultralente formulations should be suitable to provide basal insulinemia.

Original languageEnglish (US)
Pages (from-to)267-273
Number of pages7
JournalDiabetes, Nutrition and Metabolism - Clinical and Experimental
Issue number4
StatePublished - Dec 1 1991
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine (miscellaneous)
  • Food Science
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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