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Prussian blue insoluble, 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. Prussian blue insoluble 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.
Prussian blue insoluble 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 Prussian blue insoluble. (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 (137 Cs) 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 Prussian blue insoluble 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 Prussian blue insoluble treatment, the fecal to urine excretion ratio of thallium is approximately 2:1.
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 Prussian blue insoluble doses from 1 to 50 mg/day. There is little difference in radiation elimination rate between Prussian blue insoluble 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.
Table 1: Dose Response Relationship in Rats at 96 Hours
|Prussian blue insoluble Dose
|% Injected 137Cs Dose
|Untreated||58.1 (63.3 – 53.4)|
|1||9.42 (13.2 – 6.72)|
|10||1.17 (1.64 – 0.84)|
|50||0.57 (0.80 – 0.41)|
|100||0.52 (0.73 – 0.37)|
The results of fecal analysis from those patients contaminated with 137 Cs and treated with Prussian blue insoluble showed higher activities of 137 Cs in feces, and the associated whole body radioactivity counts showed a more rapid rate of elimination from the body. The effectiveness of Prussian blue insoluble for one patient is shown in Figure 1. The whole body content of radioactive material of 137 Cs 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 137 Cs during Prussian blue insoluble 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 137 Cs, after Prussian blue insoluble was stopped.
Figure 1. Comparisons of 137 Cs whole body activity
during and after Prussian blue insoluble treatment
Line A:137Cs whole body activity DURING Prussian blue
insoluble treatment at 10 gm/day.
Line B: 137Cs whole body activity AFTER Prussian insoluble ttreatment is terminated.
Dotted line: Extrapolated decrease 137Cs in whole body activity (kBq) if Prussian blue insoluble treatment was continued.
In an animal study (pigs, n = 38), after a single dose of 40 mg of labeled Prussian blue insoluble, 99% of the administered 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, Prussian blue insoluble was not significantly absorbed. Food may increase the effectiveness of Prussian blue insoluble 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 Prussian blue insoluble.
Renal Impaired and/or Compromised Liver Function Patients
Adequate and well-controlled pharmacokinetic and pharmacodynamic studies in renal impaired and/or compromised liver function patients were not identified in the literature. Prussian blue insoluble is not systemically bioavailable and does not rely on renal elimination or hepatic metabolism; therefore, the use of Prussian blue insoluble is not contraindicated in these groups of patients. However, Prussian blue insoluble 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 Prussian blue insoluble after excessive exposure to 137 Cs or non-radioactive thallium.
Overall, in literature reports, 65 patients and 7 normal human volunteers received Prussian blue insoluble after internal contamination with 137Cs.
In a 1987 incident in Goiânia, Brazil, 46 persons with heavy internal contamination with 137 Cs were treated with Prussian blue insoluble. Data on the whole body effective half-life of 137 Cs, during and after Prussian blue insoluble 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. Prussian blue insoluble reduced the mean whole-body effective half-life of 137 Cs 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 137 Cs in patients during Prussian blue insoluble treatment as compared to being off treatment.
Table 2: Cesium-137 Effective Half-life During and After
Treatment with Prussian blue Insoluble (In Days, by Age, and Dose of Prussian
Treatment –137Cs T½
|Adults||>18||10||5||26 ± 6 days||
80 ± 15 days
(all 21 adult patients)
|Adults||>18||6||10||25 ± 15 days|
|Adults||>18||3||6||25 ± 9 days|
|Adolescents||12-14||<10||5||30 ± 12 days||62 ± 14 days|
|Children||4-9||<3||7||24 ± 3 days||42 ± 4 days|
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 Prussian blue insoluble treatment.
Thirty-four patients treated with Prussian blue insoluble for non-radioactive thallium poisoning are reported in the literature. Prussian blue insoluble treatment reduced the mean serum biologic half-life of thallium from 8 days to 3 days.
Last reviewed on RxList: 10/1/2008
This monograph has been modified to include the generic and brand name in many instances.
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