Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation.

Show simple item record Yozu, Hye-Won en Khwaounjoo, Prashannata en Hill, Andrew G en Miskelly, Gordon en McKeage, Mark en 2018-10-16T22:13:01Z en 2017-06-22 en
dc.identifier.issn 2045-2322 en
dc.identifier.uri en
dc.description.abstract This study evaluated the impact of calcium and magnesium on the in vitro degradation and in vivo clearance of oxaliplatin. Intact oxaliplatin and Pt(DACH)Cl2 were measured in incubation solutions by HPLC-UV. A clinical study determined changes in plasma concentrations of calcium and magnesium in cancer patients and their impact on oxaliplatin clearance. Kinetic analyses modelled oxaliplatin degradation reactions in vitro and contributions to oxaliplatin clearance in vivo. Calcium and magnesium accelerated oxaliplatin degradation to Pt(DACH)Cl2 in chloride-containing solutions in vitro. Kinetic models based on calcium and magnesium binding to a monochloro-monooxalato ring-opened anionic oxaliplatin intermediate fitted the in vitro degradation time-course data. In cancer patients, calcium and magnesium plasma concentrations varied and were increased by giving calcium gluconate and magnesium sulfate infusions, but did not alter or correlate with oxaliplatin clearance. The intrinsic in vitro clearance of oxaliplatin attributed to chloride-, calcium- and magnesium-mediated degradation predicted contributions of <2.5% to the total in vivo clearance of oxaliplatin. In conclusion, calcium and magnesium accelerate the in vitro degradation of oxaliplatin by binding to a monochloro-monooxalato ring-opened anionic intermediate. Kinetic analysis of in vitro oxaliplatin stability data can be used for in vitro prediction of potential effects on oxaliplatin clearance in vivo. en
dc.format.medium Electronic en
dc.language eng en
dc.relation.ispartofseries Scientific reports en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.rights.uri en
dc.subject Humans en
dc.subject Chlorides en
dc.subject Calcium en
dc.subject Magnesium en
dc.subject Antineoplastic Agents en
dc.subject Kinetics en
dc.subject Oxaliplatin en
dc.title Predicting effects on oxaliplatin clearance: in vitro, kinetic and clinical studies of calcium- and magnesium-mediated oxaliplatin degradation. en
dc.type Journal Article en
dc.identifier.doi 10.1038/s41598-017-04383-4 en
pubs.issue 1 en
pubs.begin-page 4073 en
pubs.volume 7 en
dc.rights.holder Copyright: The authors en
dc.identifier.pmid 28642473 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 636057 en Medical and Health Sciences en Medical Sciences en Pharmacology en Science en Chemistry en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 2045-2322 en
pubs.record-created-at-source-date 2017-06-24 en
pubs.dimensions-id 28642473 en

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