Glucarpidase to combat toxic levels of methotrexate in patients.

摘要: In January 2012, glucarpidase (Voraxaze(®)) received approval from the US Food and Drug Administration for intravenous treatment of toxic plasma methotrexate concentrations due to impaired renal clearance. Methotrexate, an antifolate agent, has been used over 60 years in various cancers. High-dose particularly useful leukemias lymphomas. However, even with aggressive hydration urine alkalinization, such regimens can lead acute dysfunction, as indicated by decreases production concomitant increases blood urea nitrogen serum creatinine levels. Because is largely excreted kidneys, this greatly potentiate tissue damage. Toxic levels be rapidly effectively decreased administration glucarpidase. Glucarpidase a recombinant form carboxypeptidase G2, bacterial enzyme that cleaves amino acid glutamate 2,4-diamino-N(10)-methylpteroic acid. Catabolites are much less than parent compound, primarily hepatic mechanisms. available on compassionate basis since 1990s, variety case reports larger clinical trials have demonstrated safety efficacy drug patients ranging age infants elderly races ethnic groups. should not administered within 2 hours leucovorin, because agent reduced folate which competes inactivates leucovorin. Side effects rare relatively mild, include paraesthesia, flushing, nausea, vomiting, pruritus, headache. seen limited use intrathecal toxicity it also effective. Future applications chemotherapy continue active area research.