Trial reportJournal of diabetes science and technology2014
Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin.
Trial report in Journal of diabetes science and technology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Population Pharmacokinetic and Pharmacodynamic Modeling to Support Molar Dose Ratio Determination of Long-Acting Insulin Analogs.Clinical pharmacokinetics · 2026Trial
- Human regular U-500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study.Diabetes, obesity & metabolism · 2020Trial
- Treatment Patterns and Outcomes Before and After Humulin R U-500 Initiation Among US Patients with Type 2 Diabetes Previously Prescribed ≤ 200 Units/day of U-100 Insulin.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2022Article
- Pharmacokinetic-pharmacodynamic modelling of the hypoglycaemic effect of pulsatile administration of human insulin in rats.Scientific reports · 2020Article
- The Injection Technique Factor: What You Don't Know or Teach Can Make a Difference.Clinical diabetes : a publication of the American Diabetes Association · 2019Article
- U500 Disposable Patch Insulin Pump: Results and Discussion of a Veterans Affairs Pilot Study.Journal of the Endocrine Society · 2018Article
- Human Regular 500 units/mL Insulin Therapy: A Review of Clinical Evidence and New Delivery Options.Clinical diabetes : a publication of the American Diabetes Association · 2018Article
- Duration and onset of action of high dose U-500 regular insulin in severely insulin resistant subjects with type 2 diabetes.Endocrinology, diabetes & metabolism · 2018Article
- Twice-Daily vs. Once-Daily Dosing with 0.075% Bromfenac in DuraSite: Outcomes from a 14-Day Phase 2 Study.Ophthalmology and therapy · 2017Article
- Frequency-Domain Response Analysis for Quantitative Systems Pharmacology Models.CPT: pharmacometrics & systems pharmacology · 2017Article
- Indian Injection Technique Study: Population Characteristics and Injection Practices.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2017Article
- Translating U-500R Randomized Clinical Trial Evidence to the Practice Setting: A Diabetes Educator/Expert Prescriber Team Approach.The Diabetes educator · 2017Article
- Management of Severe Insulin Resistance in Patients with Type 1 Diabetes.Current diabetes reports · 2015Review
- Are you ready for more insulin concentrations?Journal of diabetes science and technology · 2015Review
- Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study.BMJ open diabetes research & care · 2015Article
- High Concentration Insulin.Indian journal of endocrinology and metabolismArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U-500R) at high doses commonly used in clinical practice (>100 units) have not been performed. The current analysis applied PK/PD modeling/simulation to fit the data and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens. Data from 3 single-dose euglycemic clamp studies in healthy obese and normal-weight patients, and normal-weight patients with type 1 diabetes were used to build the model. The model was sequential (PK inputs fed into PD component). PK was described using a 1-compartment model with first-order absorption and elimination. The model estimated separate absorption rate constants for U-500R and human regular U-100 insulin. The PD component used an effect compartment model, parameterized in terms of maximum pharmacologic effect (E(max)) and concentration to achieve 50% of E(max). The model described the data well. Steady-state PK for once-daily (QD), twice-daily (BID), or thrice-daily (TID) administration appeared to be reached 24 hours after the first dose. At steady-state, QD dosing showed the greatest fluctuations in PK/PD. BID dosing showed a gradual increase in insulin action with each dose and a fairly stable basal insulin effect. For TID dosing, activity was maintained throughout the dosing interval. PK/PD modeling/simulation of high U-500R doses supports BID or TID administration with an extended duration of activity relative to QD. TID dosing may provide slightly better full-day insulin effect. Additional PK/PD studies and randomized controlled trials of U-500R are needed to validate model predictions in patients with insulin-resistant diabetes requiring high-dose insulin.
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