Pharmacokinetic model of circulating covalent aggregates of insulin

M. Maislos, M. Bialer, P. M. Mead, D. C. Robbins

    Research output: Contribution to journalArticlepeer-review

    14 Scopus citations


    Covalent aggregates of insulin in blood of insulin-treated diabetic patients account for as much as 70% (mean 28 ± 3.6%) of serum insulin immunoreactivity. These aggregates may originate in therapeutic insulin, because similar substances account for 0.1-3% of these preparations. Larger amounts in blood imply that aggregates accumulate as a result of delayed clearance. To test and quantify this speculation, we calculated the plasma kinetics of this material in four normal volunteers who received large intravenous doses (30 mU·kg-1·min-1) of beef-pork crystalline zinc insulin for 120 min. Insulin aggregate and monomer concentrations were measured in blood samples obtained at regular intervals throughout the infusion and during 4 h after discontinuation of insulin. Pharmacokinetic parameters were calculated from the data. Insulin aggregate and monomer serum t( 1/2 ) were 63.6 ± 6.9 and 34.3 ± 2.8 min, respectively, and clearances were 101 ± 10 and 232 ± 47 ml/min. Volume of distribution (V(β)) and volume at steady state (V(ss)) were 9.1 ± 1.8 and 8.2 ± 2.2 L for insulin aggregate and 11.6 ± 2.8 and 12.2 ± 3.6 L for insulin monomer, respectively. Mean residency time was 141 ± 14 and 114 ± 10 min for insulin aggregate and monomer, respectively [P<.01 for all parameters except V(β) (.014) and V(ss) (.012), aggregate vs. monomer]. Thus, in relation to insulin monomer, calculated pharmacokinetic parameters of the aggregate predict accumulation after insulin injection. Plasma t( 1/2 ) of the aggregate was almost double that of monomeric insulin; total-body clearance and the corresponding volumes of distribution were smaller.

    Original languageEnglish
    Pages (from-to)1059-1063
    Number of pages5
    Issue number8
    StatePublished - 1 Jan 1988

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism


    Dive into the research topics of 'Pharmacokinetic model of circulating covalent aggregates of insulin'. Together they form a unique fingerprint.

    Cite this