Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes
| Autor: | Guang-Ran Yang, Jin-Kui Yang, Fan Jin, Xiu-Li Zhao, Li-Hong Shi |
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| Rok vydání: | 2014 |
| Předmět: |
Agonist
Adult Blood Glucose Male Nausea medicine.drug_class Type 2 diabetes Pharmacology Placebo Drug Administration Schedule Glucagon-Like Peptide-1 Receptor Polyethylene Glycols Young Adult Pharmacokinetics Asian People Double-Blind Method medicine Receptors Glucagon Humans Pharmacology (medical) Adverse effect Aged Glycated Hemoglobin business.industry Middle Aged medicine.disease Postprandial Period Diabetes Mellitus Type 2 Pharmacodynamics Vomiting Female medicine.symptom business Peptides |
| Zdroj: | Journal of clinical pharmacology. 55(2) |
| ISSN: | 1552-4604 |
| Popis: | This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300 μg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity. |
| Databáze: | OpenAIRE |
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