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Zn-DTPA (pentetate zinc trisodium injection) forms stable chelates with metal ions by exchanging zinc for a metal of greater binding capacity. The radioactive chelates are then excreted by glomerular fltration into the urine. In animal studies, Zn-DTPA (pentetate zinc trisodium injection) forms less stable chelates with uranium and neptunium in vivo resulting in deposition of these elements in tissues including the bone. Zn-DTPA (pentetate zinc trisodium injection) treatments are not expected to be effective for uranium and neptunium. Radioactive iodine is not bound by DTPA.
In a study of rodents internally contaminated with plutonium, the rate of plutonium elimination was measured after treatment with Ca-DTPA and Zn-DTPA (pentetate zinc trisodium injection) given intravenously as a single dose of 10 to 1,000 Ámol/kg (0.54 - 54 x maximum human dose, MHD). When treated within one hour of internal contamination, Ca-DTPA resulted in about a 10-fold higher rate of elimination of plutonium in the urine as compared to Zn-DTPA (pentetate zinc trisodium injection) . The chelating capacity of Ca-DTPA is greatest immediately and up to approximately 24 hours after internal contamination when the radiocontaminant is still circulating and readily available for chelation. After the frst dose of Ca-DTPA, maintenance treatment with either Ca-DTPA or Zn-DTPA (pentetate zinc trisodium injection) resulted in similar rates of elimination of radioactivity. However, at comparable doses, Zn-DTPA (pentetate zinc trisodium injection) had less toxicity (e.g., less depletion of trace metals, lower rate of mortality, the absence of kidney and liver vacuolization, and absence of small bowel hemorrhagic lesions).
In another study, rodents contaminated with aerosolized plutonium and americium were treated with Ca-DTPA and Zn-DTPA (pentetate zinc trisodium injection) . The treatment schedule involved inhalation of Ca-DTPA 2 Ámol/kg (0.11 MHD) 30 minutes after contamination followed by inhalation of Zn-DTPA (pentetate zinc trisodium injection) 2 Ámol/kg at approximately 6 hours, 1, 2, 3, and 6 days, then twice weekly to day 26 or day 27. The treatment regime reduced the lung deposit of plutonium and americium to 1-2% of that in untreated animals. Systemic deposit in liver and skeleton were reduced by half.
Literature and U.S. Registry data in humans indicate that intravenous administration of Zn-DTPA (pentetate zinc trisodium injection) forms chelates with radioactive contaminants found in the circulation, interstitial fuid, and tissues. When Zn-DTPA (pentetate zinc trisodium injection) is administered by inhalation, it can chelate transuranium elements. Expectoration is expected to decrease the amount of radioactive contaminant available for systemic absorption.
The effectiveness of chelation decreases with time after internal contamination because the transuranium elements become incorporated into the tissues. Chelation treatment should be given as soon as possible after known or suspected internal contamination with transuranium elements has occurred. (See DOSAGE ADMINISTRATION)
Plasma retention and urinary excretion data were obtained in 2 subjects that received 750 kBq of 14C-DTPA. As shown in Figure 1, the radiolabeled DTPA was rapidly distributed throughout the extracellular fuid space and was cleared by glomerular filtration. The plasma retention up to 7 hours post dosing was expressed by the sum of three exponential components with average half-lives of 1.4 min, 14.5 min, and 94.4 min. The level of activity in the plasma was below the limit of detection 24 hours after injection. During the study, no detectable activity was exhaled or excreted in the feces. By 24 hours, cumulative urinary excretion was more than 99% of the injected dose.
Figure 1: Percent of 14C-DTPA Distribution
Zn-DTPA (pentetate zinc trisodium injection) is poorly absorbed in the GI tract. In animal studies, after oral administration, absorption was approximately 5%. In a U.S. Registry of 18 patients who received a single inhaled or intravenous dose of 1 gram, urine data indicate that the inhaled product was absorbed and resulted in a comparable elimination of the radiocontaminant. One study of 2 human subjects that received Ca-DTPA with 14C-DTPA by inhalation revealed approximately 20% absorption from the lungs. Human or animal bioavailability comparisons for Zn-DTPA (pentetate zinc trisodium injection) are not available after administration by inhalation and intravenous injection. (See CLINICAL PHARMACOLOGY, Clinical Trials)
Following intravenous administration, Zn-DTPA (pentetate zinc trisodium injection) is rapidly distributed throughout the extracellular fuid space. No signifcant amount of Zn-DTPA (pentetate zinc trisodium injection) penetrates into erythrocytes or other cells. No accumulation of Zn-DTPA (pentetate zinc trisodium injection) in specifc organs has been observed. There is little or no binding of the chelating agent by the renal parenchyma.
Zn-DTPA (pentetate zinc trisodium injection) undergoes a minimal amount of metabolic change in the body.
Adverse Metabolic Effects
Zn-DTPA (pentetate zinc trisodium injection) results in minimal depletion of magnesium and manganese.
Zn-DTPA (pentetate zinc trisodium injection) is cleared from the plasma in the frst few hours after dosing through urinary excretion by glomerular fltration. Renal tubular excretion has not been documented. In stool samples, only a very small amount of radioactivity ( < 3%) was detected.
Renal Impaired and/or Compromised Liver Function Patients
Adequate and well-controlled pharmacokinetic and pharmacodynamic studies in renally impaired and/or hepatically impaired patients were not identifed in the literature. Both Zn-DTPA (pentetate zinc trisodium injection) and its radioactive chelates are excreted by glomerular fltration. Impaired renal function may decrease their rates of elimination and increase the serum half-life of Zn-DTPA (pentetate zinc trisodium injection) .
All clinical data has come from the treatment of individuals who were accidentally contaminated. Observational data were maintained in a U.S. Registry of individuals with internal radiation contamination primarily from acute occupational contamination with plutonium, americium and curium.
In 286 individuals, bioassays were available to measure urinary radioactivity elimination after chelation therapy. Of these 286 individuals, only 18 had matched pre-and post-chelator urine radioactivity bioassay results available. The majority of these individuals received Ca-DTPA as the initial component to their chelation therapy. When multiple chelator doses were administered over days, the standard of practice was to switch therapy to Zn-DTPA (pentetate zinc trisodium injection) following an initial dose of Ca-DTPA. Although both chelators were considered equipotent 24 hours following internal contamination, Zn-DTPA (pentetate zinc trisodium injection) was considered less toxic. In one individual who received 3 doses, 1 gram each, by nebulization (1:1 Zn-DTPA (pentetate zinc trisodium injection) and saline) followed by 6 intravenous doses, the urinary excretion of plutonium after the frst nebulized dose was increased by a factor of 45.
After initial treatment with Ca-DTPA, maintenance treatment was continued with daily 1 gram Zn-DTPA (pentetate zinc trisodium injection) doses administered over a period of days, months or years, depending on the extent of internal contamination and individual response to therapy. Treatment was generally continued until the excretion enhancement factor (EEF) approached 1. The longest treatment duration was 3.5 years. Similar increases in urinary radioactivity elimination were supported by data from the remaining 268 individuals in the U.S. Registry and from the literature.
Last reviewed on RxList: 3/9/2009
This monograph has been modified to include the generic and brand name in many instances.
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