Glucarpidase is the recombinant form of the Pseudomonas sp. (strain RS-16) enzyme carboxypeptidase G2 that is produced in Escherichia coli. In patients, glucarpidase inactivates methotrexate, and other antifolates, by hydrolyzing glutamate on the carboxyl terminal of these compounds. Therefore since methotrexate is eliminated 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®.
|Protein chemical formula||C1950H3157N543O599S7|
|Protein average weight||44016.6653 Da|
> Glucarpidase ALAQKRDNVLFQAATDEQPAVIKTLEKLVNIETGTGDAEGIAAAGNFLEAELKNLGFTVT RSKSAGLVVGDNIVGKIKGRGGKNLLLMSHMDTVYLKGILAKAPFRVEGDKAYGPGIADD KGGNAVILHTLKLLKEYGVRDYGTITVLFNTDEEKGSFGSRDLIQEEAKLADYVLSFEPT SAGDEKLSLGTSGIAYVQVNITGKASHAGAAPELGVNALVEASDLVLRTMNIDDKAKNLR FNWTIAKAGNVSNIIPASATLNADVRYARNEDFDAAMKTLEERAQQKKLPEADVKVIVTR GRPAFNAGEGGKKLVDKAVAYYKEAGGTLGVEERTGGGTDAAYAALSGKPVIESLGLPGF GYHSDKAEYVDISAIPRRLYMAARLIMDLGAGKDownload FASTA Format
|External IDs||Not Available|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
Used in patients on methotrexate treatment who have kidney dysfunction, and are experiencing an abnormally high plasma concentration of methotrexate (> 1 micromole per liter).
Glucarpidase acts as an antidote to toxic methotrexate levels by elminating methotrexate by a non-kidney route.
|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).
In healthy patients not taking methotrexate, the average maximum concentration for glucarpidase was 3.3 μg/mL.
|Volume of distribution|
Glucarpidase is likely limited to the plasma volume since its volume of distribution is 3.6 L.
Plasma protein binding was not quantified.
Metabolism was not determined.
|Route of elimination|
Route of elmination was not determined.
In healthy patients not taking methotrexate, glucarpidase has an elimination half-life of 5.6 hours. In patients with severe renal impairment (creatinine clearance <30 mL/min), glucarpidase has an longer elimination half-life at 8.2 hours.
In healthy patients not taking methotrexate, glucarpidase has a clearance of 7.5 mL/min.
Most common adverse reactions include hypotension, flushing, nausea, vomiting, headache, and paresthesia.
|Pharmacogenomic Effects/ADRs||Not Available|
|Synthesis Reference||Not Available|
|AHFS Codes||Not Available|
|FDA label||Download (367 KB)|
|MSDS||Download (83.7 KB)|
|Experimental Properties||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
|External Descriptors||Not Available|
- Small molecule
- Pharmacological action
- 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:15668713 ]
- 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:23170306 ]
- 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:23209370 ]