Erythromycin Breath Test
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The erythromycin breath test (ERMBT) is a method used to measure
metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
(oxidation and elimination from the system) by a part of the
cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
system. Erythromycin produces 14CO2, and this 14CO2 can be measured to study drugs that interact with the
cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
system.
Erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...
is tagged with
carbon-14 Carbon-14, C-14, C or radiocarbon, is a radioactive isotope of carbon with an atomic nucleus containing 6 protons and 8 neutrons. Its presence in organic matter is the basis of the radiocarbon dating method pioneered by Willard Libby and coll ...
and given as an intravenous injection; after 20 minutes the subject blows up a balloon and the
carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...
exhaled that is tagged with carbon-14 shows the activity of the
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
isoenzyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. di ...
on the erythromycin. ERMBT can be used to determine how drugs that the CYP3A4 isoenzyme metabolizes will function in a given individual. The ERMBT has been widely used and verified as a reliable method for measuring CYP3A activity in real time. Its non-invasive nature makes it useful for researching drug interactions and personalizing medicine dose for drugs metabolized by CYP3A. However, its results can vary in different clinical circumstances, emphasizing the difficulty of properly predicting drug metabolism and release. The erythromycin breath test requires an intravenous injection of 4C-N-methylerythromycin dissolved in a dextrose solution. After the injection, the patient exhales into a collection bag for 20 minutes before being bubbled through a solution containing hyamine hydroxide and a blue indicator. The blue tint fades after the solution has trapped enough carbon dioxide, indicating that it is ready for analysis. The obtained 14CO₂ is then analyzed using scintillation counting to determine the activity of the CYP3A4 enzyme in the liver. Erythromycin is a drug that treats bacterial infections like
bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
,
sexually transmitted diseases A sexually transmitted infection (STI), also referred to as a sexually transmitted disease (STD) and the older term venereal disease (VD), is an infection that is spread by sexual activity, especially vaginal intercourse, anal sex, oral ...
, and
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
. The medication is in a capsule form and takes on a "delayed-release," to ensure it is only broken down once it reaches the intestine and not by stomach acids. The erythromycin breath test has numerous clinical applications, particularly in transplantation and pharmacology. It is frequently used to evaluate the activity of the CYP3A4 enzyme, which is critical in the metabolism of medications such as cyclosporine and tacrolimus in liver transplant patients. Following surgery, the test can help predict the risk of nephrotoxicity from these drugs and assess graft function. Outside of transplantation, the ERMBT is used to investigate drug interactions, alter dosages, and track liver enzyme activity in a variety of medical conditions. The test allows doctors to determine or predict an individual's drug treatment outcome. Will a patient develop serious or fatal side effects from a certain drug? Which foods and drugs should not be taken together? With this and other tests a physician may determine treatment outcomes in advance or study the effects of new drugs. Some patients have a
congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...
inability to synthesize certain enzymes, so drugs may build up to toxic levels in their system or other drugs and foods a patient is taking may consume all of their ability to metabolize certain foods and drugs. An example is: when a person taking a cholesterol-lowering
statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...
drug then drinking grapefruit juice, they may have a poor treatment outcome (
adverse drug reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or may result from the combination of two or more drugs. The meaning of this ...
) and sustain liver damage or kidney failure due to drug induced
rhabdomyolysis Rhabdomyolysis (shortened as rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some o ...
(the breaking up of muscle tissue). The test is also used to study liver enzyme regulation under pathological conditions. Studies suggest that it could be useful in determining how chronic liver disorders like fibrosis and cirrhosis affect CYP3A function. Compared to other approaches, the ERMBT gives unique insights into CYP3A-related metabolic pathways and is less susceptible to external influences such as ethanol, making it a dependable option for monitoring liver function. The erythromycin breath test is frequently compared with other procedures for measuring CYP3A activity, like the urinary 6β-hydroxycortisol to free cortisol ratio (6β-F/FF). While both tests examine enzyme function, there are significant distinctions. The ERMBT evaluates CYP3A activity in the liver, while the 6β-F/FF ratio may indicate activity in other areas of the body, including the kidneys. As a result, the ERMBT is frequently used when a more direct assessment of liver metabolism is required.


References

{{Reflist Enzymes Breath tests