毒理性
识别：钆贝特罗用于成人及儿科患者（包括足月新生儿）的磁共振成像（MRI）中，用于检测和可视化中枢神经系统破坏的血脑屏障（BBB）区域和/或异常血管情况，并用于MRI评估恶性乳腺疾病的存度和范围。人类暴露和毒性：在给予钆维司特后，偶尔会出现心血管、呼吸或皮肤表现的范围从轻微到严重，包括死亡在内的过敏性反应和其他超敏反应。在给予钆维司特之前，要评估所有患者是否有对比剂、支气管哮喘和/或过敏性疾病的历史。这些患者可能存在对钆维司特超敏反应的增力风险。仅在能够迅速提供治疗超敏反应的人员和疗法的情况下，包括接受复苏训练的人员，才可给予钆维司特。大多数对钆维司特的超敏反应发生在给药后半小时内。延迟反应可能在给药后数天内发生。动物研究：在大鼠哺乳期研究中，钆贝特罗在乳汁中的含量低于静脉给药剂量的0.1%，且胃肠道吸收不良（大约5%的口服给药剂量在尿液中排泄）。在接受0.5 mmol/kg静脉注射[153Gd]-钆贝特罗的哺乳大鼠中，给药后3小时内，总给药放射性活性的0.01%通过母体乳汁转移给了幼崽。在给予母体有毒剂量钆贝特罗的怀孕大鼠（= 7.5 mmol/kg体重；基于体表面积相当于人类剂量的12倍）和怀孕家兔（= 2.5 mmol/kg体重；基于体表面积相当于推荐人类剂量的8倍）中，也发生了胚胎致死和胚胎发育迟缓。在家兔中，这一发现发生在没有明显母体毒性证据且胎盘转移极小的情况下（胎崽中检测到的给药剂量的0.01%）。
IDENTIFICATION: Gadobutrol is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients (including term neonates) to detect and visualize areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system and for use with MRI to assess the presence and extent of malignant breast disease. HUMAN EXPOSURE AND TOXICITY: Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist administration. Before Gadavist administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to Gadavist. Administer Gadavist only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in resuscitation. Most hypersensitivity reactions to Gadavist have occurred within half an hour after administration. Delayed reactions can occur up to several days after administration. ANIMAL STUDIES: In rat lactation studies, gadobutrol was present in milk in amounts less than 0.1% of the dose intravenously administered and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). In lactating rats receiving 0.5 mmol/kg of intravenous [153Gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk, within 3 hours after administration. Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (= 7.5 mmol/kg body weight; equivalent to12 times the human dose based on body surface area) and in pregnant rabbits (= 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses).
来源:Hazardous Substances Data Bank (HSDB)
