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DB08898 - Glucarpidase


Identification
Name Glucarpidase
Accession Number DB08898
Type biotech
Description Glucarpidase is the recombinant form of the enzyme carboxypeptidase that is produced in Esherichia coli. In patients, glucarpidase inactivates methotrexate, and other antifolates, by hydrolyzing glutamate on the carboxyl terminal of these compounds. Therefore since methotrexate is elminated enzymatically and not by the kidneys, glucarpidase is indicated in patients on methotrexate treatment who have kidney dysfunction, and are experiencing an abnormally high plasma concentration of methotrexate (>1 micromole per liter). Glucarpidase is marketed under the brand name Voraxaze(R).
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 44016.6653 g/mol
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Used in patients on methotrexate treatment who have kidney dysfunction, and are experiencing an abnormally high plasma concentration of methotrexate (> 1 micromole per liter).
Mechanism of action Glucarpidase inactivates methotrexate, and other antifolates, by hydrolyzing glutamate on the carboxyl terminal of these compounds. For methotrexate specifically, it is hydrolyzed to the inactive metabolites glutamate and 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA).
Absorption In healthy patients not taking methotrexate, the average maximum concentration for glucarpidase was 3.3 ?g/mL.
Protein binding Plasma protein binding was not quantified.
Biotransformation Metabolism was not determined.
Route of elimination Route of elmination was not determined.
Toxicity Most common adverse reactions include hypotension, flushing, nausea, vomiting, headache, and paresthesia.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Leucovorin Do not administer leucovorin within 2 hours of glucarpidase due to the fact that leucovorin is degraded by glucarpidase.
Food Interactions
  • No food effects were found.

Targets


methotrexate
Name methotrexate
Gene Name Not Available
Pharmacological action yes
Actions metabolizer
References
  • Buchen S, Ngampolo D, Melton RG, Hasan C, Zoubek A, Henze G, Bode U, Fleischhack G: Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure. Br J Cancer. 2005 Feb 14;92(3):480-7. - Pubmed
  • Tuffaha HW, Al Omar S: Glucarpidase for the treatment of life-threatening methotrexate overdose. Drugs Today (Barc). 2012 Nov;48(11):705-11. doi: 10.1358/dot.2012.48.11.1871575. - Pubmed
  • Green JM: Glucarpidase to combat toxic levels of methotrexate in patients. Ther Clin Risk Manag. 2012;8:403-13. doi: 10.2147/TCRM.S30135. Epub 2012 Nov 22. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
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