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RADIOGARDASE(Heyl Chem.-pharm. Fabrik GmbH & Co. KG)(二)
in enterohepatic recirculation. Without Prussian blue insoluble treatment, the fecal to urine excretion ratio of thallium is approximately 2:1.
Based on the mechanisms of action, Prussian blue insoluble may bind other elements (e.g., potassium), and cause electrolyte or other nutritional imbalances. (See PRECAUTIONS, Laboratory Tests.)
Dose-Response Relationship
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 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 (mg/day) % Injected 137 Cs Dose Remaining (Range)
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 g 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.
(click image for full-size original)
Figure 1. Comparisons of 137 Cs whole body activity during and after Prussian blue insoluble treatment.
Line A: 137 Cs whole body activity (kBq) DURING Prussian blue insoluble treatment at 10 g/day.
Line B: 137 Cs whole body activity (kBq) AFTER Prussian blue insoluble treatment is terminated.
Dotted line: Extrapolated decrease in 137 Cs whole body activity (kBq) if Prussian blue insoluble treatment was continued.
Pharmacokinetics
Absorption/Elimination
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 Effects
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 imp |
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