Effect of Omeprazole on Metformin
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Effect of Omeprazole, an OCT Inhibitor, on the Pharmacodynamics and Pharmacokinetics of Metformin, Involved the Mechanism of Attenuating AMPK Phosphorylation|
- Whether the pharmacokinetics of metformin would be effected by omeprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]Pharmacokinetic parameters such as the area under the concentration-time curve (AUC), the elimination half-life(t½) and maximum metformin concentration (Cmax)
- Whether the pharmacodynamics of metformin would be effected by omeprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]oral glucose tolerance tests (OGTTs) before and after receiving two doses of metformin
|Study Start Date:||September 2012|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
oral dose of Placebo combined with two dose of Metformin (OGTTs)
oral dose of Omeprazole (80 mg) combined with two dose of Metformin (OGTTs)
Other Name: PPI
Metformin is the most widely used drug for the treatment of type 2 diabetes. This insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but also on the cardiovascular system. The antihyperglycemic effect of metformin is mainly based on suppression of hepatic gluconeogenesis by activation of AMP-activated protein kinase (AMPK), which suppresses glucagon-stimulated glucose production and causes an increase in glucose uptake in muscle and in hepatic cells. Metformin is actively transported across membranes. The organic cation transporter 1 (OCT1) is responsible for uptake of metformin in hepatocytes, which is an essential step in reducing hepatic glucose production. , which is closely associated with its pharmacological action/adverse reactions.
However, metformin alone is thought to be insufficient for achieving good metabolic control. Thus, treatment in addition to metformin is often required. Sitagliptin attenuates metformin-mediated AMPK phosphorylation through inhibition of organic cation transporters PPIs are frequently used in metformin-treated patients with metabolic syndrome and cardiovascular diseases. Moreover, gastroesophageal reflux disease (GERD) is commonly seen in patients with type 2 diabetes and proton-pump inhibitors (PPIs) are the drugs of best choice in treatment of GERD. These data support the hypothesis that proton pump inhibitors can be used to treat type II diabetes. Moreover, PPIs itself appears to has significant glucose-lowering effects in an animal model of type 2 diabetes regardless of whether metformin is administered concurrently.
A recent in-vitro study found that PPI inhibit metformin uptake by organic cation transporters (OCTs). This drug-drug interaction the clinical has the potential relevance of consequences on metformin disposition and/or efficacy. Since there is a possibility for the combined use of metformin and omeprazole in chronic diabetics, the study is planned to investigate the effect of nicorandil on the activity of gliclazide in normal and diabetic rats to evaluate effectiveness of the combination.
The study is planned to find the pharmacodynamics and pharmacokinetics of metformin in the presence of omeprazole in healthy subjects and to evaluate the mechanisms of the interaction if occurs.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01711320
|Department of pharmacy, Xijing Hospital, Fourth Military Medical University|
|Xi'an, Shaanxi, China|
|Study Chair:||AiDong Wen, Pro||Department of pharmacy, Xijing Hospital, Fourth Military Medical University|