Optiray Mechanism of Action

Therapeutic or Pharmacological Classification: Non-ionic, low osmolality, water soluble radiopaque contrast medium for intravascular use.
Pharmacology: General: The pharmacokinetics of Optiray (ioversol) in normal subjects conform to an open two compartment model with first order elimination (a rapid alpha phase of 6.8 minutes for drug distribution and a slower beta phase of 92 minutes, for drug elimination). Based on the blood clearance curves for 12 healthy volunteers (6 receiving 50 mL and 6 receiving 150 mL of Optiray 320), the biological half-life was 1.5 hours for both dose levels and there was no evidence of any dose related difference in the rate of elimination. The mean half-life for urinary excretion following a 50 mL dose was 118 minutes (105-156) and following a 150 mL dose was 105 minutes.
Optiray is excreted mainly through the kidneys following intravascular administration. Fecal elimination is 3-9%. Approximately 50% of the injected dose is excreted at 1.5 hours and 86% at 48 hours; about 1.5% is retained, mostly by the thyroid and liver. In patients with impaired renal function and in infants with immature kidneys, the elimination half-life is prolonged. In patients with severe renal disease, excretion does not occur. Optiray does not notably bind to serum or plasma proteins to any marked extent and no significant metabolism, deiodination or biotransformation occurs.
Optiray, like all other contrast media, may induce changes in thyroid function in some patients, and elevation of thyroxine and/or TSH may be observed.
Optiray, like other non-ionic contrast media, has an insignificant effect on blood coagulation (as shown by slightly increased prothrombin time and partial thromboplastin time, and delayed platelet aggregation) and does not possess the anti-coagulant properties of ionic contrast media.
Optiray causes concentration-dependent hemolysis, aggregation and crenation of red blood cells.
Elevations of several laboratory parameters (AST, ALT, LDH, bilirubin, creatinine and BUN) following intravascular administration have been reported in several patients which were not considered clinically significant.
Intravascular: Intravascular injection of Optiray opacifies those vessels in the path of flow of the contrast bolus, permitting their radiographic visualization.
Following intravenous contrast medium administration, the increase in density in non-neural tissue is dependent on the presence of iodine in the vascular and extravascular (extra cellular) compartments. This is related to the rate and amount of contrast material administered, blood flow, vascularity, capillary permeability, extravascular effusion and renal filtration.
Peak iodine blood levels occur immediately following rapid intravenous administration, then fall rapidly as the contrast medium is diluted in the plasma volume and diffuses from the vascular into the extravascular spaces. Equilibration between plasma and extravascular iodine concentration occurs within a few minutes.
Contrast enhancement (increase in the difference in density between adjacent tissues) is the result of differential vascular and extravascular iodine concentration between normal and abnormal tissues, which may accentuate inherent differences in pre-existent tissue density. With contrast enhancement a pathological lesion may demonstrate increased or decreased density compared to the surrounding normal tissue. Some lesions, however, will remain or become isodense and thus undetectable by attempted contrast enhancement. Contrast enhancement in most cases is greatest immediately after bolus injection.
Optiray may be visualized in the renal parenchyma within 30-60 seconds following rapid intravenous injection. Opacification of the calyces and pelves in patients with normal renal function becomes apparent within 1-3 minutes, with optimum contrast occurring within 5-15 minutes.
In nephropathic conditions, particularly when excretory capacity has been altered, the rate of excretion varies unpredictably, and opacification may be delayed for up to several hours after injection. Severe renal impairment may result in a lack of diagnostic opacification of the urinary tract, and depending on the degree of renal impairment, prolonged plasma ioversol levels may be anticipated in these patients as well as in infants with immature kidneys.
Optiray (33% l) was compared in intra-carotid studies in 45 anesthetized rats to iopamidol (32% l) and iohexol (30% l). There was no detectable damage to the blood-brain barrier with any of these substances.
Generally, less warmth and pain are associated with the injection of Optiray than with conventional ionic media. Comparative studies using diatrizoate and iothalamate showed significantly less heat sensation and pain with Optiray. Other non-ionic agents, iohexol and iopamidol, gave results similar to Optiray.
Optiray had significantly less effect on cardiovascular and ECG parameters than did diatrizoate. For example, it produced significantly less bradycardia, tachycardia, T-wave changes, ST depression, ST elevation and hypotension than were seen with diatrizoate.
Computerized Tomography: CT Scanning of the Head: In brain scanning, the contrast medium does not accumulate in normal brain tissue due to the presence of the blood-brain barrier. The increase in X-ray absorption in the normal brain is due to the presence of the contrast agent within the blood pool. A break in the blood-brain barrier, such as occurs in malignant tumors of the brain allows accumulation of the contrast medium within the interstitial tumor tissue; adjacent normal brain tissue does not retain the contrast medium.
Rapid infusion of the dose yields peak blood iodine concentrations immediately following infusion (within 15 to 120 seconds), which fall rapidly over the next 5 to 10 minutes.
Diagnostic contrast enhancement images of the brain have been obtained up to 1 hour after intravenous bolus administration.
CT Scanning of the Body: During CT of the body, Optiray (ioversol) diffuses rapidly from the vascular to the extra-vascular space. Increase in X-ray absorption is related to blood flow, concentration of the contrast medium and extraction of the contrast medium by interstitial tissue. Contrast enhancement is thus due to the relative differences in extra-vascular diffusion between normal and abnormal tissue - a situation quite different from that in the brain.
Contrast enhancement appears to be greatest immediately after bolus infusion (15 to 120 seconds).
Utilization of a continuous scanning technique (dynamic CT scanning) may improve enhancement of tumor and other lesions, such as an abscess.