Biological markers and diagnostic tests for angiotensin converting enzyme inhibitor and vasopeptidase inhibitor-associated angioedema

a technology of vasopeptidase inhibitor and angioedema, which is applied in the field of biological markers and diagnostic tests for angioedema associated with angioedema, can solve the problems of increasing the chances of a subject developing angioedema, inability to accurately predict which subjects are at risk, and african americans are particularly susceptible to ace inhibitor associated angioedema. , to achieve the effect of reducing the activity of the sampl

Inactive Publication Date: 2005-08-18
VANDERBILT UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the administration of an ACE and / or a vasopeptidase inhibitor (referred to herein as an ACE / vasopeptidase inhibitor) is contraindicated for subjects with a history of angioedema due to the potential severity of this side effect, which can be so severe as to result in death.
Also, these inhibitors are often administered over long periods of time because the illnesses that they treat are often chronic conditions.
This could increase the chances of a subject developing angioedema over a course of treatment.
Currently, it is not possible to accurately predict which subjects are at risk to develop angibedema when taking an ACE or vasopeptidase inhibitor; however it is known that approximately 0.1% to 1.0% or more of the subjects receiving an ACE or vasopeptidase inhibitor will develop angioedema as a side effect.
For example, African Americans are particularly susceptible to ACE inhibitor associated angioedema.
In patients who develop angioedema while taking one of these medications, it is difficult to determine if the angioedemic condition arose in response to the medication or due to some other occurrence.
Most practitioners, however, consider these alternative therapies to be less effective in treating the original condition than ACE / vasopeptidase inhibitor therapy.

Method used

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  • Biological markers and diagnostic tests for angiotensin converting enzyme inhibitor and vasopeptidase inhibitor-associated angioedema
  • Biological markers and diagnostic tests for angiotensin converting enzyme inhibitor and vasopeptidase inhibitor-associated angioedema
  • Biological markers and diagnostic tests for angiotensin converting enzyme inhibitor and vasopeptidase inhibitor-associated angioedema

Examples

Experimental program
Comparison scheme
Effect test

example 2

Illustrative Example 2

[0161] A 64-year-old African American man with dilated cardiomyopathy and a history of congestive heart failure presents to the emergency room with swelling of his lips and oropharynx. On examination he is noted to be stridorous and he is intubated to protect his airway. He is given intravenous corticosteroids and histamine H1 and H2 antagonists. Prior to admission he was taking the diuretic furosemide, the ACE inhibitor lisinopril, and the aldosterone receptor antagonist spironolactone. He has taken the ACE inhibitor for at least four years and has never had any previous episode of angioedema. Five days prior to admission he was started on the antibiotic ciprofloxacin for a urinary tract infection. It was not clear to the patient's physician whether his angioedema was related to his use of an ACE inhibitor. Given the proven benefit of ACE inhibitors as treatment in patients with left ventricular dysfunction, the physician desired to continue therapy, if possib...

example 3

Illustrative Example 3

[0166] A physician determines that a patient is in need of treatment with an ACE / vasopeptidase inhibitor. A blood sample is drawn from the patient and is processed to obtain a serum sample. The DPP IV and / or APP activity is determined for the individual. The patient is started on the inhibitor(s). The DPP IV and / or APP enzyme activity is checked periodically to determine the risk for angioedema and to determine if the risk is changing. The period between tests can be any period selected by the physician. In certain examples the period is about one week, in certain examples the period is about six months and in certain examples the period varies from test to test.

example 4

Illustrative Example 4

[0167] Example 4 is the same as Example 3, except that the patient develops angioedema during the course of treatment with the inhibitor(s). Treatment with the inhibitor(s) is suspended until the angioedema is resolved and until the DPP IV and / or APP enzyme activity is found to be at a safe level(s) to resume treatment with the inhibitor(s).

LABORATORY EXAMPLES

[0168] The following Laboratory Examples have been included to illustrate preferred modes of the invention. Certain aspects of the following Laboratory Examples are described in terms of techniques and procedures found or contemplated by the present inventors to work well in the practice of the invention. These Laboratory Examples are exemplified through the use of standard laboratory practices of the inventors. In light of the present disclosure and the general level of skill in the art, those of skill will appreciate that the following Laboratory Examples are intended to be exemplary only and that nume...

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Abstract

Deficiencies in certain physiological pathways are linked with ACE or vasopeptidase inhibitor associated angioedema. Additionally, detection and / or measurement of dipeptidyl peptidase IV (DPP IV) enzyme activity and aminopeptidase P (APP) enzyme activity is a predictor of this risk. The present invention provides biological markers, diagnostic tests, and pharmaceutical indications that are useful in the diagnosis and treatment of angioedema and in the marketing and safety of certain medications. This ability can be important for the treatment of a subject that is in need of or are taking an angiotensin-converting enzyme (ACE) inhibitor and / or a vasopeptidase inhibitor (combined ACE and neutral endopeptidase (NEP) inhibitor), which are commonly used in the treatment of hypertension (high blood pressure), diabetes, and cardiac and renal diseases.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present patent application is based on and claims priority to U.S. Provisional Application Ser. No. 60 / 244,524, entitled “Biological. Markers and Diagnostic Tests for Angiotensin Converting Enzyme Inhibitor and Vasopeptidase Inhibitor Associated Angioedema”, which was filed Oct. 31, 2000 and is incorporated herein by reference.GRANT STATEMENT [0002] This invention was made with federal grant money under NIH grants HL56963, GM 07569 and 5M01 RR-00095. Thus, the United States Government has certain rights in the present invention.TECHNICAL FIELD [0003] The present invention relates generally to screening tests to determine which patients are at risk for developing angioedema associated with inhibitors of angiotensin converting enzyme (ACE) and / or combined ACE and neutral endopeptidase (NEP) inhibitors (a combined ACE / NEP inhibitor is referred to herein as a “vasopeptidase inhibitor”). More particularly, the present invention relates t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/37
CPCC12Q1/37
Inventor BROWN, NANCY
Owner VANDERBILT UNIV
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