Pharmacokinetics of the Rapid-Acting Insulin Analog, Insulin Aspart, in Rats, Dogs, and Pigs, and Pharmacodynamics of Insulin Aspart in Pigs
Abstract
The objective of this study was to compare the pharmacokinetics and pharmacodynamics of insulin aspart (IA), a rapidly acting insulin analog, with those of human soluble (regular) insulin (HI) in animal models after s.c. and i.v. dosing. Single doses of IA and HI were administered i.v. and s.c. to rats and dogs at three dose levels, and at one dose level to pigs; rats and dogs also underwent repeated s.c. dosing for 1 week. Plasma insulin levels were assessed at predetermined time points after dosing; plasma glucose levels were measured in pigs only. There were no significant pharmacokinetic differences between IA and HI after a single s.c. or i.v. dose in rats or dogs, and no differences were observed after repeated s.c. dosing, implying there was no accumulation. In pigs, there was a strong trend toward more rapid absorption of IA compared with HI after s.c. dosing, whereas there were no differences after i.v. administration. After s.c. dosing in pigs, IA produced significantly lower plasma glucose levels compared with HI during the period 30 to 75 min after dosing (P <.05). In conclusion, IA was more rapidly absorbed than HI after s.c. administration only in the pig; this difference was reflected in earlier and more pronounced effects on plasma glucose levels.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This observation is consistent with published animal studies, human clinical trials, and routine clinical care.
“This observation is consistent with published animal studies, human clinical trials, and routine clinical care.5,6,22,23”
From Detailed Analysis of Insulin Absorption Variability and the Tissue Response to Continuous Subcutaneous Insulin Infusion Catheter Implantation in Swine (2017) · cites this paper as [22]
Cites
WANG, P. (1993) · The Lancet · doi:10.1016/0140-6736(93)90816-y · Cited by 446 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis
Umpierrez, G. E., Jones, S., Smiley, D., Mulligan, P., Keyler, T., Temponi, A., Semakula, C., Umpierrez, D., Peng, L., Cerón, M., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0169 · Cited by 120 · see citing works
El-Khatib, F. H., Jiang, J., & Damiano, E. R. (2007) · Journal of Diabetes Science and Technology · doi:10.1177/193229680700100208 · Cited by 99 · see citing works
Review of evidence for adult diabetic ketoacidosis management protocols
Tran, T. T. T., Pease, A., Wood, A. J., Zajac, J. D., Mårtensson, J., Bellomo, R., & Ekinci, E. I. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00106 · Cited by 97 · see citing works
Hauzenberger, J. R., Hipszer, B. R., Loeum, C., McCue, P. A., DeStefano, M., Torjman, M. C., Kaner, M. T., Dinesen, A. R., Chervoneva, I., Pieber, T. R., et al. (2017) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2017.0175 · Cited by 39 · see citing works
“This observation is consistent with published animal studies, human clinical trials, and routine clinical care.(5,6,22,23) Of interest, the CCs produced the fastest insulin absorption, the highest plasma insulin concentration, and the greatest AUC60 on day 5 of implantation.”
Result
- Authors
- Plum, A., Agersø, H., & Andersen, L.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Plum, Anne
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 28
- Issue
- 2
- Pages
- 155-160
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W2245370565
- Cited by
- 56
- References
- 1
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2017: 8 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- insulin aspart, rapid-acting insulin analogs, pharmacokinetics, pharmacodynamics, subcutaneous administration, intravenous administration, plasma insulin, plasma glucose, subcutaneous absorption, cross-species comparison, rats, dogs, pigs
- MeSH terms
- Animals, Blood Glucose, Dogs, Female, Half-Life, Humans, Hypoglycemia, Hypoglycemic Agents, Injections, Intravenous, Injections, Subcutaneous, Insulin, Male, Species Specificity, Swine, Rats, Sprague-Dawley, Area Under Curve, Rats, Insulin Aspart
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
