Pharmacology Of Gadopentetate dimeglumine

Indication	For use with magnetic resonance imaging (MRI) in adults, and pediatric patients (2 years of age and older) to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues as well as lesions with abnormal vascularity in the head and neck. Also used to facilitate the visualization of lesions with abnormal vascularity in the body (excluding the heart).
Pharmacodynamics	Not Available
Mechanism of action	Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. MR images are based primarily on proton density and proton relaxation dynamics. MR instruments are sensitive to two different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and T2 (spin-spin or transverse relaxation time). Paramagnetic agents contain one or more unpaired electrons that enhance the T1 and T2 relaxation rates of protons in their molecular environment. The proton relaxation effect (PRE) of an unpaired electron is 700 times stronger than that of a proton itself. In MRI, visualization of normal and pathological brain tissue depends in part on variations in the radio frequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadopentetate dimeglumine shortens the T1 and T2 relaxation times in tissues where it accumulates. In the central nervous system (CNS), gadopentetate dimeglumine enhances visualization of normal tissues that lack a blood-brain barrier, such as the pituitary gland and the meninges. Gadopentetate dimeglumine does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in CNS lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadopentetate dimeglumine in lesions such as neoplasms, abscesses, and subacute infarcts. Outside the CNS, gadopentetate dimeglumine rapidly reaches equilibrium in the interstitial compartment and enhances signal in all tissues as a function of delivery and size of the interstitial compartment. This compound has also been found to inhibit human erythrocyte 6-phosphogluconate dehydrogenase.
Absorption	Not Available
Volume of distribution	266 ± 43 mL/kg
Protein binding	Not Available
Metabolism	No detectable biotransformation or decomposition.
Route of elimination	Gadopentetate is exclusively eliminated in the urine with 83 ± 14% (mean ± SD) of the dose excreted within 6 hours and 91 ± 13% (mean ± SD) by 24 hours, post-injection.
Half life	Distribution half life 12 minutes, elimination half 100 minutes
Clearance	1.94 +/- 0.28 mL/min/kg [Normal subjects]
Toxicity	Not Available

Pharmacology Of Gadobenate Dimeglumine

Indication	Gadobenate Dimeglumine is an MRI contrast agent used primarily for MR imaging of the liver. It can also be used for MRI of the heart, as well as and central nervous system in adults to visualize lesions with abnormal brain vascularity or abnormalities in the blood brain barrier, the brain, spine, or other associated tissues.
Pharmacodynamics	Gadobenate dimeglumine shares the pharmacokinetic properties of the ECF contrast agent gadopentetate dimeglumine; however, gadobenate differs in that is also selectively taken-up by hepatocytes and excreted via the bile (up to 5% of dose). The elimination half-life of gadobenate dimeglumine is approximately 1 hour. It is not metabolized.
Mechanism of action	Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed, its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record 2 different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and the T2 (spin-spin or transverse relaxation time). In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in the T2. When placed in a magnetic field, Gadobenate Dimeglumine shortens both the T1 and the T2 relaxation times in tissues where it accumulates. At clinical doses, Gadobenate Dimeglumine primarily affects the T1 relaxation time, thus producing an increase in signal intensity. Gadobenate Dimeglumine does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars).
Absorption	Not Available
Volume of distribution	Not Available
Protein binding	Plasma protein binding is low, weak, and transient.
Metabolism	Not metabolized.
Route of elimination	Gadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine.
Half life	1 hour
Clearance	0.093 +/- 0.010 L/hr/kg [healthy male subjects receiving 3 single-dose IV administration with doses from 0.005-0.4 mmol/kg]
Toxicity	Gadolinium-based radiocontrast agents like gadobenate dimeglumine are cytotoxic to renal cells. The toxic effects include apoptosis, cellular energy failure, disruption of calcium homeostasis, and disturbance of tubular cell polarity, and are thought to be linked to oxidative stress.

Pharmacology Of Gadoteridol

Indication	Gadoteridol is an MRI contrast agent used for contrast enhancement of the brain, spine and surrounding tissues resulting in improved visualization (compared with unenhanced MRI) of lesions with abnormal vascularity or those thought to cause a disruption of the normal blood brain barrier. Gadoteridol can also be used for whole body contrast enhanced MRI including the head, neck, liver, breast, musculoskeletal system and soft tissue pathologies.
Pharmacodynamics	Not Available
Mechanism of action	Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record two different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and T2 (spin-spin or transverse relaxation time). In MRI, visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadoteridol shortens the T1 relaxation time in tissues where it accumulates. Gadoteridol does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadoteridol in lesions such as neoplasms, abscesses, and subacute infarcts.
Absorption	Not Available
Volume of distribution	204 ± 58 mL/kg
Protein binding	Not Available
Metabolism	Not Available
Route of elimination	Gadoteridol is eliminated in the urine with 94.4 ± 4.8% (mean ± SD) of the dose excreted within 24 hours post-injection.
Half life	Distribution 12 minutes (mean), elimination 100 minutes (mean).
Clearance	1.50+/- 0.35 mL/ min/kg renal cl=1.41 +/- 0.33 mL/ min/kg
Toxicity	Not Available

Pharmacology Of Gadoversetamide

Indication	Gadoversetamide is an MRI contrast agent used for MRI diagnostic procedures to provide increased enhancement and visualization of lesions of the brain, spine and liver, including tumors.
Pharmacodynamics	Not Available
Mechanism of action	Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. MR images are based primarily on proton density and proton relaxation dynamics. MR instruments are sensitive to two different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and T2 (spin-spin or transverse relaxation time). Paramagnetic agents contain one or more unpaired electrons that enhance the T1 and T2 relaxation rates of protons in their molecular environment. In MRI, visualization of normal and pathological brain, spinal and hepatic tissue depends in part on variations in the radio frequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in T2. When placed in a magnetic field, gadoversetamide shortens the T1 and T2 relaxation times in tissues where it accumulates. At the recommended dose, the effect is primarily on T1 relaxation time, and produces an increase in signal intensity (brightness). Gadoversetamide does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in CNS lesions that may have a normal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadoversetamide in lesions such as neoplasms, abscesses, and subacute infarcts.
Absorption	Not Available
Volume of distribution	162 ± 25 mL/kg [normal subjects]
Protein binding	Not Available
Metabolism	None detected
Route of elimination	The mean cumulative urinary excretion of gadoversetamide at 72 hours was approximately 93.5% for renal impaired patients and 95.8% for subjects with normal renal function
Half life	Distribution 13.3 ± 6.8 (mean) minutes, elimination 103.6 ± 19.5 (mean) minutes.
Clearance	72 +/- 16.3 mL/hr/kg [healthy]
Toxicity	Not Available

Pharmacology Of Diatrizoate

Indication	Used, alone or in combination, for a wide variety of diagnostic imaging methods, including angiography, urography, cholangiography, computed tomography, hysterosalpingography, and retrograde pyelography. It can be used for imaging the gastrointestinal tract in patients allergic to barium.
Pharmacodynamics	Diatrizoate is the most commonly used water-soluble, iodinated, radiopaque x-ray contrast medium. Radiopaque agents are drugs used to help diagnose certain medical problems. They contain iodine, which blocks x-rays. Depending on how the radiopaque agent is given, it localizes or builds up in certain areas of the body. The resulting high level of iodine allows the x-rays to make a "picture" of the area. The areas of the body in which the radiopaque agent localizes will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.
Mechanism of action	Diatrizoate is an iodine-containing X-ray contrast agent. Iodated contrast agents were among the first contrast agents developed. Iodine is known to be particular electron-dense and to effectively scatter or stop X-rays. A good contrast agent requires a high density of electron-dense atoms. Therefore, the more iodine, the more "dense" the x-ray effect. Iodine based contrast media are water soluble and harmless to the body. These contrast agents are sold as clear colorless water solutions, the concentration is usually expressed as mg I/ml. Modern iodinated contrast agents can be used almost anywhere in the body. Most often they are used intravenously, but for various purposes they can also be used intraarterially, intrathecally (the spine) and intraabdominally - just about any body cavity or potential space.
Absorption	Not Available
Volume of distribution	Not Available
Protein binding	Not Available
Metabolism	Not Available
Route of elimination	However, it is not metabolized but excreted unchanged in the urine, each diatrizoate molecule remaining "obligated" to its sodium moiety. The liver and small intestine provide the major alternate route of excretion for diatrizoate. Injectable radiopaque diagnostic agents are excreted unchanged in human milk. Saliva is a minor secretory pathway for injectable radiopaque diagnostic agents.
Half life	Not Available
Clearance	Not Available
Toxicity	High osmolal radiocontrast agents like diatrizoate are cytotoxic to renal cells. The toxic effects include apoptosis, cellular energy failure, disruption of calcium homeostasis, and disturbance of tubular cell polarity, and are thought to be linked to oxidative stress.

Pharmacology Of Gadodiamide

Indication	For intravenous use in MRI to visualize lesions with abnormal vascularity (or those thought to cause abnormalities in the blood-brain barrier) in the brain (intracranial lesions), spine, and associated tissues.
Pharmacodynamics	Not Available
Mechanism of action	Based on the behavior of protons when placed in a strong magnetic field, which is interpreted and transformed into images by magnetic resonance (MR) instruments. Paramagnetic agents have unpaired electrons that generate a magnetic field about 700 times larger than the proton's field, thus disturbing the proton's local magnetic field. When the local magnetic field around a proton is disturbed, its relaxation process is altered. MR images are based on proton density and proton relaxation dynamics. MR instruments can record 2 different relaxation processes, the T1 (spin-lattice or longitudinal relaxation time) and the T2 (spin-spin or transverse relaxation time). In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with changes in proton density, alteration of the T1, and variation in the T2. When placed in a magnetic field, gadodiamide shortens both the T1 and the T2 relaxation times in tissues where it accumulates. At clinical doses, gadodiamide primarily affects the T1 relaxation time, thus producing an increase in signal intensity. Gadodiamide does not cross the intact blood-brain barrier; therefore, it does not accumulate in normal brain tissue or in central nervous system (CNS) lesions that have not caused an abnormal blood-brain barrier (e.g., cysts, mature post-operative scars). Abnormal vascularity or disruption of the blood-brain barrier allows accumulation of gadodiamide in lesions such as neoplasms, abscesses, and subacute infarcts.
Absorption	Not Available
Volume of distribution	200 ± 61 mL/kg
Protein binding	Not Available
Metabolism	There is no detectable biotransformation or decomposition of gadodiamide.
Route of elimination	Gadodiamide is eliminated primarily in the urine.
Half life	Two-compartment model with mean distribution and elimination half-lives (reported as mean ± SD) of 3.7 ± 2.7 minutes and 77.8 ± 16 minutes, respectively.
Clearance	Renal cl=1.7 mL/min/kg Plasma cl=1.8 mL/min/kg
Toxicity	Not Available