Battelle, Pacific Northwest Division, Richland, WA 99352, USA.
Health Phys. 2011 Aug;101(2):118-27. doi: 10.1097/HP.0b013e318208ceb6.
Cuprimine® and Syprine® are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.
铜绿假单胞菌®和 Syprine®是经美国食品和药物管理局批准的治疗药物，用于治疗威尔逊病（一种铜转运的遗传缺陷）中的铜过载，通过螯合和加速内部沉积的铜的排泄。这些口服治疗药物基于各自的活性成分 D-青霉胺（DPA）和 N，N'-双（2-氨基乙基）-1,2-乙二胺二盐酸盐（Trien）。铜绿假单胞菌被认为是主要治疗药物，尽管医生越来越多地将 Syprine 作为一线治疗药物。这两种药物均表现出口服全身活性和低毒性；它们的生物学效应和安全性已得到确立。以前使用啮齿动物动物模型的体内研究确立了 Cuprimine 和 Syprine 对（60）Co 和（210）Po 的脱壳潜力。目前，这些研究正在扩大，以评估这些药物对几种额外放射性核素的体内脱壳功效。在本报告中，使用放射性核素（137）Cs、（60）Co、（192）Ir 和（85）Sr 讨论了这项研究的结果。进行了为期 48 小时的短期试点研究，以评估 DPA 和 Trien 对雄性 Wistar-Han 大鼠体内脱壳潜力。在这些研究中，通过静脉内（IV）注射向动物给予放射性核素溶液，然后单次静脉内给予 DPA 或 Trien。对照动物仅接受放射性核素。结果表明，在评估的时间范围内，DPA 有效地脱除（60）Co。DPA 和 Trien 对（137）Cs 和（85）Sr 的脱除也分别适度有效。研究未发现 DPA 或 Trien 对（192）Ir 的脱除有效。基于这些令人鼓舞的发现，有必要进行进一步的研究来评估暴露于放射性核素后螯合剂给药的剂量反应谱和时间。
