Erythromycin breath test

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Erythromycin breath test
Purposemeasure oxidation and elimination from the system

The erythromycin breath test (ERMBT) is a method used to measure metabolism (oxidation and elimination from the system) by a part of the cytochrome P450 system. [1] Erythromycin produces 14CO2, and this 14CO2 can be measured to study drugs that interact with the cytochrome P450 system. [2] Erythromycin is tagged with carbon-14 and given as an intravenous injection; after 20 minutes the subject blows up a balloon and the carbon dioxide exhaled that is tagged with carbon-14 shows the activity of the CYP3A4 isoenzyme 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. [3]

The erythromycin breath test requires an intravenous injection of [14C-N-methyl]-erythromycin 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. [4]

Erythromycin is a drug that treats bacterial infections like bronchitis, sexually transmitted diseases, and pneumonia. 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. [5] 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. [6]

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. [1]

Some patients have a congenital 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 drug then drinking grapefruit juice, they may have a poor treatment outcome (adverse drug reaction) and sustain liver damage or kidney failure due to drug induced rhabdomyolysis (the breaking up of muscle tissue). [7]

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. [8]

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. [9]

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<span class="mw-page-title-main">Cimetidine</span> Medication

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<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 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 oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">CYP2D6</span> Human liver enzyme

Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.

<span class="mw-page-title-main">CYP2E1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.

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Naringin is a flavanone-7-O-glycoside between the flavanone naringenin and the disaccharide neohesperidose. The flavonoid naringin occurs naturally in citrus fruits, especially in grapefruit, where naringin is responsible for the fruit's bitter taste. In commercial grapefruit juice production, the enzyme naringinase can be used to remove the bitterness (debittering) created by naringin. In humans naringin is metabolized to the aglycone naringenin by naringinase present in the gut.

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

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<span class="mw-page-title-main">Grapefruit–drug interactions</span> Drug interactions with grapefruit juice

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<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

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<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

<span class="mw-page-title-main">CYP2B6</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CYP3A5</span> Enzyme involved in drug metabolism

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<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

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The LiMAx test (maximum liver function capacity) is a dynamic liver function test based on the metabolism of 13C-methacetin by the liver-specific cytochrome P450 1A2 system. The test can be carried out at bedside displaying actual liver function at the point of measurement (Point-of-care testing).

<span class="mw-page-title-main">Epoxydocosapentaenoic acid</span> Group of chemical compounds

Epoxide docosapentaenoic acids are metabolites of the 22-carbon straight-chain omega-3 fatty acid, docosahexaenoic acid (DHA). Cell types that express certain cytochrome P450 (CYP) epoxygenases metabolize polyunsaturated fatty acids (PUFAs) by converting one of their double bonds to an epoxide. In the best known of these metabolic pathways, cellular CYP epoxygenases metabolize the 20-carbon straight-chain omega-6 fatty acid, arachidonic acid, to epoxyeicosatrienoic acids (EETs); another CYP epoxygenase pathway metabolizes the 20-carbon omega-3 fatty acid, eicosapentaenoic acid (EPA), to epoxyeicosatetraenoic acids (EEQs). CYP epoxygenases similarly convert various other PUFAs to epoxides. These epoxide metabolites have a variety of activities. However, essentially all of them are rapidly converted to their corresponding, but in general far less active, vicinal dihydroxy fatty acids by ubiquitous cellular soluble epoxide hydrolase. Consequently, these epoxides, including EDPs, operate as short-lived signaling agents that regulate the function of their parent or nearby cells. The particular feature of EDPs distinguishing them from EETs is that they derive from omega-3 fatty acids and are suggested to be responsible for some of the beneficial effects attributed to omega-3 fatty acids and omega-3-rich foods such as fish oil.

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In biochemistry, cytochrome P450 enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. As of 2018, more than 300,000 distinct CYP proteins are known.

References

  1. 1 2 Zhou S, Chan E, Lim LY, et al. (October 2004). "Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4". Curr. Drug Metab. 5 (5): 415–42. doi:10.2174/1389200043335450. PMID   15544435.
  2. ↑ Chhun, Stephanie (2009). "Gefitinib-phenytoin interaction is not correlated with the 14 C-erythromycin breath test in healthy male volunteers". British Journal of Clinical Pharmacology. 68 (2): 226–237. doi:10.1111/j.1365-2125.2009.03438.x. PMC   2767287 . PMID   19694743.
  3. ↑ Chiou, Win L.; Jeong, Hyun Young; Wu, Ta C.; Ma, Chien (October 2001). "Use of the erythromycin breath test for in vivo assessments of cytochrome P4503A activity and dosage individualization". Clinical Pharmacology & Therapeutics. 70 (4): 305–310. doi:10.1016/S0009-9236(01)45600-1. ISSN   0009-9236.
  4. ↑ Salvat, Cécile; Mouly, Stéphane; Rizzo‐Padoin, Nathalie; Knellwolf, Anne‐Laure; Simoneau, Guy; Duet, Michèle; Nataf, Valérie; Bailliart, Olivier; Bergmann, Jean‐François (June 2003). "The [ 14 C‐N‐methyl]‐erythromycin breath test dosimetry complies with the French regulations for radiation safety". Fundamental & Clinical Pharmacology. 17 (3): 349–353. doi:10.1046/j.1472-8206.2003.00139.x. ISSN   0767-3981.
  5. ↑ "Erythromycin: MedlinePlus Drug Information". medlineplus.gov. Retrieved 2022-05-08.
  6. ↑ Schmidt, Lars E.; Rasmussen, Allan; Kirkegaard, Preben; Dalhoff, Kim (2003-07-27). "Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients1". Transplantation. 76 (2): 358–363. doi:10.1097/01.TP.0000076626.46866.E7. ISSN   0041-1337.
  7. ↑ Lee, Jonathan W.; Morris, Joan K.; Wald, Nicholas J. (2016-01-01). "Grapefruit Juice and Statins". The American Journal of Medicine. 129 (1): 26–29. doi:10.1016/j.amjmed.2015.07.036. ISSN   0002-9343. PMID   26299317.
  8. ↑ Kolars, Joseph C.; Murray, Scott A.; Peters, Ken M.; Watkins, Paul B. (December 1990). "Differential regulation of liver P-450III cytochromes in choline-deficient rats: Implications for the erythromycin breath test as a parameter of liver function". Hepatology. 12 (6): 1371–1378. doi:10.1002/hep.1840120619. ISSN   0270-9139.
  9. ↑ Watkins, Paul B; Turgeon, D Kim; Saenger, Paul; Lown, Kenneth S; Kolars, Joseph C; Hamilton, Ted; Fishman, Kenneth; Guzelian, Philip S; Voorhees, John J (September 1992). "Comparison of urinary 6-β-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity". Clinical Pharmacology and Therapeutics. 52 (3): 265–273. doi:10.1038/clpt.1992.140. ISSN   0009-9236.
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