CLINICAL PHARMACOLOGY
Intravascular injection of a radiopaque diagnostic agent opacifies those vessels in the path of the flow of the contrast medium, permitting radiographic visualization of the internal structures of the human body until significant hemodilution occurs.
Following intravascular injection, HEXABRIX is rapidly transported through the circulatory system to the kidneys and is excreted unchanged in the urine. The pharmacokinetics of intravascularly administered radiopaque contrast media are usually best described by a two compartment model with a rapid alpha phase for drug distribution and a slower beta phase for drug elimination. In 10 patients with normal renal function, the alpha and beta half-lives of HEXABRIX were 12 (4-17) and 92 (61-140) minutes, respectively. Following the intravenous administration of 50 mL of HEXABRIX in 10 normal volunteers, the mean peak plasma concentration occurred at two (1-3) minutes, reaching a concentration of 2.1 (1.8-2.8) mg/mL. Approximately 50 (42-67) percent of the intravenously administered dose was recovered in the urine at two hours, and 90 (68-105) percent was recovered at 24 hours.
The joint spaces as well as the uterus and fallopian tubes may be visualized by the direct injection of the contrast medium into the region to be studied.
Injectable iodinated contrast agents are excreted either through the kidneys or through the liver. These two excretory pathways are not mutually exclusive, but the main route of excretion seems to be related to the affinity of the contrast medium for serum albumin. Ioxaglate salts are poorly bound to serum albumin, and are excreted mainly through the kidneys.
The liver and small intestine provide the major alternate route of excretion. In patients with severe renal impairment, the excretion of this contrast medium through the gallbladder and into the small intestine sharply increases.
Ioxaglate salts cross the placental barrier in humans and are excreted unchanged in human milk.
CT SCANNING OF THE HEAD
When used for contrast enhancement in computed tomographic head imaging, the degree of enhancement is directly related to the amount of iodine administered. Rapid injection of the entire dose yields peak blood iodine concentrations immediately following the injection, which falls rapidly over the next five to ten minutes as a result of dilution in the vascular and extravascular fluid compartments. Equilibration is reached in about ten minutes and thereafter the fall in iodine plasma concentration becomes exponential.
In brain scanning, contrast media do not accumulate in normal brain tissue due to the blood brain barrier (BBB). The increase in x-ray attenuation usually seen in normal tissue following contrast medium injection is due to the presence of the contrast medium in the blood pool. Disruption in the BBB, such as occurs in malignant tumors of the brain, allows accumulation of contrast medium within the interstitial tumor tissue; adjacent normal brain tissue does not contain the contrast medium. Maximum contrast enhancement frequently occurs after peak blood iodine levels are reached. A delay in maximum contrast enhancement can occur depending on the peak iodine level achieved and the cell type of the lesion. This lag in enhancement is probably associated with the accumulation of the contrast medium within the lesion and outside the blood pool.
The image enhancement of non-tumor lesions, such as arteriovenous malformations and aneurysms, is dependent on the iodine content of the circulating blood pool.
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