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
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
Based on the mechanisms of action, Prussian blue insoluble may bind other elements
(e.g., potassium), and cause electrolyte or other nutritional imbalances. (See
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
||58.1 (63.3 – 53.4)
||9.42 (13.2 – 6.72)
||1.17 (1.64 – 0.84)
||0.57 (0.80 – 0.41)
||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
||26 ± 6 days
80 ± 15 days
(all 21 adult patients)
||25 ± 15 days
||25 ± 9 days
||30 ± 12 days
||62 ± 14 days
||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.