ArticlePharmaceutical research2016
Addition of 20-kDa PEG to Insulin Lispro Alters Absorption and Decreases Clearance in Animals.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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.
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Who cites it
6 citing papers in PubMed.
- Classification system proposed to guide the design, development, regulatory approval, and scaling of long acting, small- and macro-molecule parenteral products (CS-BLAP).Journal of pharmaceutical sciences · 2026Review
- Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic ModulationBiomacromolecules · 2021Article
- Engineering biopharmaceutical formulations to improve diabetes management.Science translational medicine · 2021Review
- A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs.Nature biomedical engineering · 2020Article
- Multivalent Presentation of Peptide Targeting Groups Alters Polymer Biodistribution to Target Tissues.Biomacromolecules · 2018Article
- Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect on Variability.Journal of diabetes research · 2018Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDetermine the pharmacokinetics of insulin peglispro (BIL) in 5/6-nephrectomized rats and study the absorption in lymph duct cannulated (LDC) sheep.
methodsBIL is insulin lispro modified with 20-kDa linear PEG at lysine B28 increasing the hydrodynamic size to 4-fold larger than insulin lispro. Pharmacokinetics of BIL and insulin lispro after IV administration were compared in 5/6-nephrectomized and sham rats. BIL was administered IV or SC into the interdigital space of the hind leg, and peripheral lymph and/or serum samples were collected from both LDC and non-LDC sheep to determine pharmacokinetics and absorption route of BIL.
resultsThe clearance of BIL was similar in 5/6-nephrectomized and sham rats, while the clearance of insulin lispro was 3.3-fold slower in 5/6-nephrectomized rats than in the sham rats. In non-LDC sheep, the terminal half-life after SC was about twice as long vs IV suggesting flip-flop pharmacokinetics. In LDC sheep, bioavailability decreased to <2%; most of the dose was absorbed via the lymphatic system, with 88% ± 19% of the dose collected in the lymph after SC administration.
conclusionThis work demonstrates that increasing the hydrodynamic size of insulin lispro through PEGylation can impact both absorption and clearance to prolong drug action.
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Registered trials
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