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Single-dose pharmacokinetics and glucodynamics of the novel, long-acting basal insulin LY2605541 in healthy subjects.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2014 Jul; Vol. 54 (7), pp. 792-9. Date of Electronic Publication: 2014 Feb 13. - Publication Year :
- 2014
-
Abstract
- LY2605541 is a novel basal insulin analog with a prolonged duration of action. Two Phase I studies assessed LY2605541 pharmacokinetics (PK), glucodynamics (GD), and tolerability in healthy subjects. In Study 1, 33 subjects received single subcutaneous (SC) doses of LY2605541 (0.01-2.22 U/kg) and insulin glargine (0.5-0.8 U/kg) followed by euglycemic clamp for up to 24-36 hours. In Study 2, absolute bioavailability of SC LY2605541 was assessed in 8 subjects by comparing dose normalized area under concentration versus time curve of SC against IV administration. Time-to-maximum plasma concentration (medians) and geometric means for half-life (t½ ) and apparent clearance, respectively, ranged from 18.0 to 42.0 hours, 24.4-45.5 hours, and 1.8-2.8 L/h for SC LY2605541, versus 10.0-12.0 hours, 12.2-14.9 hours, and 51.4-65.2 L/h for SC insulin glargine. LY2605541 glucose infusion rate (GIR) profiles were sustained for ≥36 hours versus glargine GIR profiles, which waned at 24 hours. After IV administration, LY2605541's geometric mean t½ was 2.3 hours. LY2605541 intra-subject variability (CV%) was <18% for PK and <32% for GD parameters. The most common adverse events were related to study procedures and were mild-moderate in severity. These results established a well-tolerated baseline dose for LY2605541 with a relatively flat PK profile and low intra-subject variability.<br /> (© 2014, The American College of Clinical Pharmacology.)
- Subjects :
- Adult
Biological Availability
Cohort Studies
Cross-Over Studies
Dose-Response Relationship, Drug
Drugs, Investigational administration & dosage
Drugs, Investigational adverse effects
Drugs, Investigational analysis
Female
Glucose Clamp Technique
Half-Life
Humans
Hypoglycemic Agents administration & dosage
Hypoglycemic Agents adverse effects
Hypoglycemic Agents blood
Infusions, Intravenous
Injections, Subcutaneous
Insulin Glargine
Insulin Lispro administration & dosage
Insulin Lispro adverse effects
Insulin Lispro blood
Insulin, Long-Acting administration & dosage
Insulin, Long-Acting adverse effects
Insulin, Long-Acting blood
Insulin, Long-Acting pharmacokinetics
Male
Metabolic Clearance Rate
Middle Aged
Polyethylene Glycols administration & dosage
Polyethylene Glycols adverse effects
Reproducibility of Results
Young Adult
Blood Glucose analysis
Drugs, Investigational pharmacokinetics
Hypoglycemic Agents pharmacokinetics
Insulin Lispro pharmacokinetics
Polyethylene Glycols pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 54
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24504686
- Full Text :
- https://doi.org/10.1002/jcph.276