Ignite Creation Date:
2025-12-25 @ 3:48 AM
Ignite Modification Date:
2025-12-26 @ 2:35 AM
Study NCT ID:
NCT00668902
Status:
COMPLETED
Last Update Posted:
2014-12-17
First Post:
2008-01-17
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole
Sponsor:
Indiana University
Organization:
Study Overview
Official Title:
Rapid Screening Phenotype Test To Evaluate CYP 2C19 Enzyme Activity Using Stable Isotope [13C]Pantoprazole
Status:
COMPLETED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine the function of an enzyme that breaks down drugs and helps the removal of drugs from your body. This enzyme is called cytochrome P450 2C19 and is located in your liver. Exposure to other medications or variations in genes that you have inherited from your parents, may speed up or slow the function of this enzyme. As a result, some patients may develop unwanted effects from a drug while some other patients may not get benefit from taking the same drug. The aim of this study is to determine the function of this enzyme in your liver. We will do this by performing a series of breath tests and blood samples after you take pantoprazole. Pantoprazole is approved as an oral and intravenous drug by the Food and Drug Administration (FDA).
Detailed Description:
The goal of this study is to develop a quick and reliable method that will diagnose hepatic CYP2C19 function and could be used routinely in clinical practice. Specifically, we propose to test pantoprazole - 13C as a probe for determining CYP2C19 phenotype. Pantoprazole, 5-(difluoromethoxy)-2-\[\[(3,4-dimethoxy-2-pyridyl)-methyl\]sulfinyl\]-1H -benzimidazole, is a substituted benzimidazole sulfoxide and a selective and long-acting proton pump inhibitor. This drug is widely used clinically in the treatment of severe gastroesophageal reflux disease, and for treatment of duodenal and gastric ulceration. Pantoprazole is extensively metabolized in the liver, with almost 80% of an oral or intravenous dose is excreted as metabolites in urine. The main metabolite is formed by O-demethylation at the 4-position of the pyridine ring by CYP2C19, followed by conjugation with sulphate (M2), while pantoprazole sulfone formed by CYP3A represents a minor metabolic pathway(20). The critical role of CYP2C19 in the in vivo clearance of the drugs is further demonstrated by the fact that healthy volunteers that are PMs of this enzyme achieve approximately 6-fold higher pantoprazole exposure than those who are extensive metabolizers of CYP2C19(20). This concept proposal exploits the use of the 13C-label that is incorporated at the O-methyl site of pantoprazole, which specifically designed for the CYP2C19-mediated O-demethylation (Figure 1). Then, during catalysis, CYP2C19-pantoprazole reaction in the liver results in the release of 13CO2 which is then eliminated from the body via the lung expired breath. The subsequent quantification of 13CO2 allows indirect determination of the hepatic CYP2C19 enzyme and thus the pharmacokinetics of its substrates. The salient features of the 13C-breath test means that this test would be non-invasive, non-radioactive, safe and simple. The protocol in general can be performed rapidly (one hour or less after pantoprazole administration) and can be determined directly at the point of care (e.g., hospitals and physicians' offices) using relatively inexpensive instrumentation (UBiT-IR300IR spectrometer; Meretek), and patients do not require waiting for hours or days for diagnostic results. This test may be particularly important to probe the activity of CYP2C19 for infants, children, pregnant and lactating women, seniors averse to the use of needles or in poor health and subjects scared of blood draws.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: