Identification
NameGlucarpidase
Accession NumberDB08898
TypeBiotech
GroupsApproved
Description

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 structureDb08898
Related Articles
Protein chemical formulaC1950H3157N543O599S7
Protein average weight44016.6653 Da
Sequences
> Glucarpidase
ALAQKRDNVLFQAATDEQPAVIKTLEKLVNIETGTGDAEGIAAAGNFLEAELKNLGFTVT
RSKSAGLVVGDNIVGKIKGRGGKNLLLMSHMDTVYLKGILAKAPFRVEGDKAYGPGIADD
KGGNAVILHTLKLLKEYGVRDYGTITVLFNTDEEKGSFGSRDLIQEEAKLADYVLSFEPT
SAGDEKLSLGTSGIAYVQVNITGKASHAGAAPELGVNALVEASDLVLRTMNIDDKAKNLR
FNWTIAKAGNVSNIIPASATLNADVRYARNEDFDAAMKTLEERAQQKKLPEADVKVIVTR
GRPAFNAGEGGKKLVDKAVAYYKEAGGTLGVEERTGGGTDAAYAALSGKPVIESLGLPGF
GYHSDKAEYVDISAIPRRLYMAARLIMDLGAGK
Download FASTA Format
Synonyms
Carboxypeptidase G2
Folate hydrolase G2
Glutamate carboxypeptidase
Pteroylmonoglutamic acid hydrolase G2
External IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VoraxazeInjection, powder, for solution1000 [USP'U]/1IntravenousBtg International Inc2012-04-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII2GFP9BJD79
CAS number9074-87-7
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).

Structured Indications
Pharmacodynamics

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).

TargetKindPharmacological actionActionsOrganismUniProt ID
MethotrexateSmall moleculeyes
metabolizer
Humannot applicabledetails
Related Articles
Absorption

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.

Protein binding

Plasma protein binding was not quantified.

Metabolism

Metabolism was not determined.

Route of elimination

Route of elmination was not determined.

Half life

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.

Clearance

In healthy patients not taking methotrexate, glucarpidase has a clearance of 7.5 mL/min.

Toxicity

Most common adverse reactions include hypotension, flushing, nausea, vomiting, headache, and paresthesia.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
LeucovorinThe serum concentration of the active metabolites of Leucovorin can be reduced when Leucovorin is used in combination with Glucarpidase resulting in a loss in efficacy.Approved
LevoleucovorinThe serum concentration of the active metabolites of Levoleucovorin can be reduced when Levoleucovorin is used in combination with Glucarpidase resulting in a loss in efficacy.Approved
Food Interactions
  • No food effects were found.
References
Synthesis ReferenceNot Available
General References
  1. 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 ]
  2. 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 ]
External Links
ATC CodesV03AF09
AHFS CodesNot Available
PDB Entries
FDA labelDownload (367 KB)
MSDSDownload (83.7 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentChemotherapeutic Agent Toxicity / Malignant Lymphomas / Mucositis / Neurotoxicity1
1, 2TerminatedSupportive CareMalignancies, Hematologic / Tumors, Solid1
2CompletedTreatmentNeoplasms1
2TerminatedTreatmentSarcoma, Osteogenic1
2TerminatedTreatmentSarcoma, Osteogenic / Spindle Cell Sarcoma of Bone1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Lymphocytic Leukemia (ALL)1
Not AvailableApproved for MarketingNot AvailableNeoplasms1
Not AvailableCompletedSupportive CareNeurotoxicity / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous1000 [USP'U]/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
metabolizer
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
Drug created on June 04, 2013 22:24 / Updated on August 17, 2016 12:24