Insoluble Prussian blue, ferric(III) hexacyanoferrate(II), after oral ingestion is not absorbed through the intact gastrointestinal wall. Its clearance from the body depends on the gastrointestinal tract transit time. Insoluble Prussian blue acts by ion-exchange, adsorption, and mechanical trapping within the crystal structure and has a very high affinity for radioactive and non-radioactive cesium and thallium.

Insoluble Prussian blue binds cesium and thallium isotopes in the gastrointestinal tract after these isotopes are ingested or excreted in the bile by the liver thereby reducing gastrointestinal reabsorption (enterohepatic circulation). In studies of rats, pigs, and dogs that were internally contaminated with cesium and thallium, the presence of the insoluble complexes in the gastrointestinal lumen, changed the primary elimination route from the kidney to the feces and increased the rate of elimination of these two contaminants.

The rate of cesium and thallium elimination was proportional to the duration and dose of insoluble Prussian blue. (See CLINICAL PHARMACOLOGY, Pharmacokinetics.) A radioactive element has a constant rate of disintegration that is reflected by its physical half-life. The rate of element elimination from the body is reflected by its biologic half-life. The combined rate of radiation disintegration and rate of element elimination is reflected by the effective half-life.

Cesium-137 (¹³⁷Cs) has a physical half-life of 30 years with a beta energy peak at 174.0 keV. Following entry into the blood, it is distributed uniformly through all body tissues. Approximately 10% of cesium is eliminated rapidly with a biological half-life of 2 days and 90% is eliminated more slowly, with a biological half-life of 110 days. Less than 1% of the cesium was retained with a longer biological half-life of about 500 days. Cesium follows the movement of potassium and is excreted into the intestine, reabsorbed from the gut into the blood, then to the bile, where it is excreted again into the gut (enterohepatic circulation). Without insoluble Prussian blue treatment, ~80% of cesium is excreted through the kidneys and ~20% in the feces. Because of cesium’s long physical half-life, the rate of radiation elimination is similar to the rate of element elimination from the body.

Thallium-201 (²⁰¹Tl) has a physical half-life of 3 days with electron and photon emissions with a gamma energy peak at 167.4 keV. Following entry into the blood, thallium is distributed in the kidneys (3%) and all other organs (97%). Non-radioactive thallium, depending upon the tissue, has a biological half-life of 8-10 days. Thallium also follows the movement of potassium and is excreted by the bile in enterohepatic recirculation. Without insoluble Prussian blue treatment, the fecal to urine excretion ratio of thallium is approximately 2:1.

Based on the mechanisms of action, insoluble Prussian blue may bind other elements (e.g., potassium), and cause electrolyte or other nutritional imbalances. (See PRECAUTIONS, Laboratory Tests.)

Animal Data: Dose-response studies have not been conducted in human subjects. In a study using rats (n=40, mean body weight range of 188-219 g) injected with ¹³⁷Cs it was demonstrated that there is a dose response relationship of the amount of radiation elimination with insoluble Prussian blue doses from 1 to 50 mg/day. There is little difference in radiation elimination rate between insoluble Prussian blue doses of 50 to 100 mg/day. In Table 1, the % of Injected Radiation Dose Remaining is defined as the percentage of the total injected dose of ¹³⁷Cs remaining in the body at 96 hours post administration.

Human Data: The results of fecal analysis from those patients contaminated with ¹³⁷Cs and treated with insoluble Prussian blue showed higher activities of ¹³⁷Cs in feces, and the associated whole body radioactivity counts showed a more rapid rate of elimination from the body. The effectiveness of insoluble Prussian blue for one patient is shown in Figure 1. The whole body content of radioactive material of ¹³⁷Cs in kilo-Bequerels (kBq) is on the y-axis. Time in days is on the x-axis. Line "A" represents the whole body activity of ¹³⁷Cs during insoluble Prussian blue treatment at 10 gm daily. The dotted line represents extrapolation of the whole body activity if treatment was continued. Line "B" represents the whole body activity of ¹³⁷Cs, after insoluble Prussian blue was stopped.

Line A: ¹³⁷Cs whole body activity (kBq) DURING insoluble Prussian blue treatment at 10 gm/day.

Line B: ¹³⁷Cs whole body activity (kBq) AFTER insoluble Prussian blue treatment is terminated.

Dotted line: Extrapolated decrease in ¹³⁷Cs whole body activity (kBq) if insoluble Prussian blue treatment was continued.

In an animal study (pigs, n= 38), after a single dose of 40 mg of labeled insoluble Prussian blue, 99% of the administered insoluble Prussian blue dose was excreted unchanged in feces. Absorption from multiple doses has not been studied.

Food effect studies were not identified in the literature. In animal studies, insoluble Prussian blue was not significantly absorbed. Food may increase the effectiveness of insoluble Prussian blue by stimulating bile secretion.

Food is known to increase bile production and enterohepatic circulation. The increase in enterohepatic circulation may increase the amount of cesium and thallium in the gastrointestinal lumen, and may increase the amounts available for binding with insoluble Prussian blue.

Adequate and well-controlled pharmacokinetic and pharmacodynamic studies in renal impaired and/or compromised liver function patients were not identified in the literature. Insoluble Prussian blue is not systemically bioavailable and does not rely on renal elimination or hepatic metabolism; therefore, the use of insoluble Prussian blue is not contraindicated in these groups of patients. However, insoluble Prussian blue may be less effective in patients with impaired liver function due to decreased excretion of cesium and thallium in the bile.

Epidemiological studies and literature review data were reported in 106 subjects who received insoluble Prussian blue after excessive exposure to ¹³⁷Cs or non-radioactive thallium.

Overall, in literature reports, 65 patients and 7 normal human volunteers received insoluble Prussian blue after internal contamination with ¹³⁷Cs.

In a 1987 incident in Goiânia, Brazil, 46 persons with heavy internal contamination with ¹³⁷Cs were treated with insoluble Prussian blue. Data on the whole body effective half-life of ¹³⁷Cs during and after insoluble Prussian blue treatment was completed on 33/46 of these patients. The untreated mean whole body effective half-life of ¹³⁷Cs is 80 days in adults, 62 days in adolescents, and 42 days in children. Insoluble Prussian blue reduced the mean whole body effective half-life of ¹³⁷Cs by 69% in adults, by 46% in adolescents and by 43% in children. The following table shows the decrease in whole body effective half-life of ¹³⁷Cs in patients during insoluble Prussian blue treatment as compared to being off treatment.

Data from additional literature articles including a study of 7 human volunteers contaminated with trace doses of ¹³⁷Cs and reports on 19 patients contaminated with ¹³⁷Cs in other incidents, show a similar reduction in whole body effective half-life after insoluble Prussian blue treatment.

Thirty-four patients treated with insoluble Prussian blue for non-radioactive thallium poisoning are reported in the literature. Insoluble Prussian blue treatment reduced the mean serum biologic half-life of thallium from 8 days to 3 days.

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