Iobitridol (trade name Xenetix) is a pharmaceutical drug used as an iodine-based

radiocontrast agent Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography (contrast CT), projectional radiography, and fluoroscopy. Radiocontrast agents are typically iod ...

X-ray imaging Radiography is an imaging technology, imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical ("diagnostic" radiog ...

. It is injected into blood vessels, joints, or body cavities such as the

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

, and filtered out by the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

s. Its most common adverse effect is

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

. Severe allergic reactions are rare. The drug received its first marketing approval in 1994 in France and is approved for use in many European countries including the UK, but not in the US. It is manufactured by Guerbet.

Medical uses

Iobitridol is used for intravenous urography (imaging of the

urinary system The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, urinary bladder, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume ...

via a vein),

angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...

(imaging of blood vessels), angiocardiography (heart and

coronary arteries The coronary arteries are the arteries, arterial blood vessels of coronary circulation, which transport oxygenated blood to the Cardiac muscle, heart muscle. The heart requires a continuous supply of oxygen to function and survive, much like any ...

arthrography An arthrogram is a series of images of a joint after injection of a contrast medium, usually done by fluoroscopy or MRI. The injection is normally done under a local anesthetic such as Novocain or lidocaine. The radiologist or radiographer perfor ...

(joints),

hysterosalpingography Hysterosalpingography (HSG), also known as uterosalpingography, is a radiology, radiologic procedure to investigate the shape of the uterine cavity and the shape and patency of the fallopian tubes. It is a special x-ray procedure using Contrast ...

(

and

fallopian tubes The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive sy ...

), and imaging of the

cranium The skull, or cranium, is typically a bony enclosure around the brain of a vertebrate. In some fish, and amphibians, the skull is of cartilage. The skull is at the head end of the vertebrate. In the human, the skull comprises two prominent ...

and the whole body. It is approved for use in adults and children.

Contraindications

The drug is contraindicated in people with manifest hyperthyreosis because of its

iodine Iodine is a chemical element; it has symbol I and atomic number 53. The heaviest of the stable halogens, it exists at standard conditions as a semi-lustrous, non-metallic solid that melts to form a deep violet liquid at , and boils to a vi ...

content. It must not be used to image the uterus or fallopian tubes in pregnant women.

Adverse effects

Iobitridol is generally well tolerated. The only side effect observed in more than 1% of patients is

. Rare side effects (in fewer than 1 per 10.000 people) include

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

(severe allergic reactions),

circulatory collapse Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, tachycardia, hyperventilation, sweating, anxiety, and increased thirst. ...

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

-related effects, and skin reactions such as

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

. Rare side effects in brain imaging include

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

s, transient sight disorders, memory loss, and

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

.Xenetix 300 (300 mgI/ml) Solution for Injection: . Accessed 2021-03-18.

Overdose

Overdosing is unlikely. It is managed by rehydration therapy and monitoring of the kidney function for at least three days. If necessary, iobitridol can be removed from the body by

haemodialysis Hemodialysis, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as c ...

Interactions

Drug interactions are the same as with other iodine-containing contrast agents: patients taking

diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

are at a higher risk of developing kidney failure under iobitridol unless they receive a water and

electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...

infusion before imaging. As the

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

drug

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, ...

is eliminated via the kidneys, it is recommended that people with severe kidney impairment should pause metformin during and after they are given iobitridol. Certain

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...

(blood pressure lowering) drugs such as

beta-blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention) ...

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

s, and

sartan Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s can prevent the heart from compensating for low blood pressure, with an increased risk of circulatory collapse.

Iodine-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nu ...

, a radioactive

isotope Isotopes are distinct nuclear species (or ''nuclides'') of the same chemical element. They have the same atomic number (number of protons in their Atomic nucleus, nuclei) and position in the periodic table (and hence belong to the same chemica ...

used for thyroid imaging (

scintigraphy Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally a ...

) and therapy of

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, ...

s, can be less effective when used within several weeks after the application of iobitridol because of residual iodine in the body.

Interleukin 2 Interleukin-2 (IL-2) is an interleukin, which is a type of cytokine signaling molecule forming part of the immune system. It is a 15.5–16 Dalton (unit), kDa protein that regulates the activities of white blood cells (leukocytes, often ...

cancer therapy has been thought to result in more severe side effects than iobitridol, but a 2009 literature search has found no such risk.

Pharmacology

Mechanism of action

Iobitridol is an iodine-containing

. The iodine atoms readily absorb

X-rays An X-ray (also known in many languages as Röntgen radiation) is a form of high-energy electromagnetic radiation with a wavelength shorter than those of ultraviolet rays and longer than those of gamma rays. Roughly, X-rays have a wavelength ran ...

, resulting in better contrast in

radiography Radiography is an imaging technology, imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical ("diagnostic" radiog ...

images. The quality of images made with this drug is equally good as with other low– or medium–

osmolarity Osmotic concentration, formerly known as osmolarity, is the measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution (osmol/L or Osm/L). The osmolarity of a solution is usually expressed as Osm/ ...

iodinated

contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...

s such as

iopamidol Iopamidol (INN), sold under the brand name Isovue among others, is a nonionic, low-osmolar iodinated contrast agent, developed by Bracco Diagnostics. It is available in various concentrations, from 200 to 370 mgI/mL. Medical uses Iopamidol is i ...

iohexol Iohexol, sold under the trade name Iodaque among others, is a contrast agent used for X-ray imaging. This includes when visualizing arteries, veins, ventricles of the brain, the urinary system, and joints, as well as during computed tomograph ...

Pharmacokinetics

After

intravenous infusion Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

, iobitridol is distributed in the

circulatory system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...

and the

interstitium In anatomy, the interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this s ...

. The substance is only marginally bound to blood

plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

s (to about 2%) and

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

s because the

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

side chains of the molecule efficiently mask the central iodinated

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

ring. It is not

metabolized 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 ...

but eliminated in the unchanged form via the kidneys by

glomerular filtration ''Glomerulus'' (; : glomeruli) is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin Latin ( or ) is a classical language belonging to the I ...

without active secretion or reabsorption. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

is 1.8 hours. In people with kidney failure, the substance is instead eliminated via the

bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior). Bile is requ ...

Chemistry

Of the molecular mass, 45.6% is contributed by the three iodine atoms. Iobitridol is

nonionic An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

but water-soluble, having some OH groups in its side chains designed to mask the central

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

benzene ring. The solution has a low osmolarity of 695 (''Xenetix 300'') or 915 mOsm/kg H₂O (''Xenetix 350''), which means it causes fewer allergic and allergy-like reactions, as well as less

extravasation Extravasation is the leakage of a fluid out of its contained space into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells through the capillary wall, ...

(leakage of blood vessels) than contrast agents with higher osmolarities.

References

{{Contrast media Radiocontrast agents Iodobenzene derivatives Benzamides Anilides