{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:55:32Z","timestamp":1791572132114,"version":"4.3.4"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T00:00:00Z","timestamp":1381968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Study Objective<\/jats:title>\n                    <jats:p>Because the incidence rate of renal impairment is 2\u201310% for patients treated with high\u2010dose methotrexate and renal impairment develops in 0\u201312.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Pooled analysis of efficacy data from four multicenter single\u2010arm compassionate\u2010use clinical trials using protocols from 1993 to 2007.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high\u2010dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1\u00a0\u03bcmol\/L and one postglucarpidase methotrexate concentration measurement by high\u2010performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>\n                      Efficacy was defined as rapid and sustained clinically important reduction (\n                      <jats:styled-content style=\"fixed-case\">RSCIR<\/jats:styled-content>\n                      ) in plasma methotrexate concentration, with a concentration of 1\u00a0\u03bcmol\/L or lower at all postglucarpidase determinations. Median age of efficacy\u2010evaluable patients was 20\u00a0years (range 5\u00a0weeks\u201384\u00a0years). Osteosarcoma (36%), non\u2010Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7\u00a0\u03bcmol\/L. At the first (median 15\u00a0minutes) through the last (median 40\u00a0hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction.\n                      <jats:styled-content style=\"fixed-case\">RSCIR<\/jats:styled-content>\n                      was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5\u00a0days after glucarpidase administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/phar.1360","type":"journal-article","created":{"date-parts":[[2013,10,17]],"date-time":"2013-10-17T04:22:59Z","timestamp":1381983779000},"page":"427-439","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Efficacy of Glucarpidase (Carboxypeptidase\n                    <scp>G<\/scp>\n                    2) in Patients with Acute Kidney Injury After High\u2010Dose Methotrexate Therapy"],"prefix":"10.1002","volume":"34","author":[{"given":"Brigitte C.","family":"Widemann","sequence":"first","affiliation":[{"name":"National Cancer Institute Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalini","family":"Jayaprakash","sequence":"additional","affiliation":[{"name":"National Cancer Institute Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbin","family":"Christensen","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"St. Jude Children's Research Hospital Memphis Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Chauhan","sequence":"additional","affiliation":[{"name":"BTG International Inc. 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