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Th1136 details
Primary information
ID1623
ThPP IDTh1136
Therapeutic Peptide/Protein NameGlucarpidase
SequenceALAQKRDNVLFQAATDEQPAVIKTLEKLVNIETGTGDAEGIAAAGNFLEA view full sequnce in fasta
Functional ClassificationIc
Molecular Weight44016.6653
Chemical FormulaC1950H3157N543O599S7
Isoelectric PointN.A.
HydrophobicityN.A.
Melting Point (℃)N.A.
Half LifeElimination half-life of 5.6 hours
DescriptionRecombinant (E. Coli derived) form of the Pseudomonas sp. (strain RS-16) enzyme, carboxypeptidase G2. It inactivates methotrexate and other antifolates by hydrolyzing glutamate on the carboxyl terminal of these compounds. 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).
Indication/DiseaseUsed in patients on methotrexate treatment who have kidney dysfunction, and are experiencing an abnormally high plasma concentration of methotrexate (> 1 micromole per liter).
PharmacodynamicsGlucarpidase acts as an antidote to toxic methotrexate levels by elminating methotrexate by a non-kidney route.
Mechanism of ActionGlucarpidase 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).
ToxicityMost common adverse reactions include hypotension, flushing, nausea, vomiting, headache, and paresthesia.
MetabolismMetabolism was not determined.
AbsorptionIn healthy patients not taking methotrexate, the average maximum concentration for glucarpidase was 3.3 μg/mL.
Volume of DistributionGlucarpidase is likely limited to the plasma volume since its volume of distribution is 3.6 L.
ClearanceIn healthy patients not taking methotrexate, glucarpidase has a clearance of 7.5 mL/min.
CategoriesEnzymes
Patents NumberN.A.
Date of IssueN.A.
Date of ExpiryN.A.
Drug InteractionN.A.
TargetMethotrexate
Information of corresponding available drug in the market
Brand NameVoraxaze
CompanyBTG International
Brand DiscriptionVORAXAZE (glucarpidase) is a carboxypeptidase produced by recombinant DNA technology in genetically modified Escherichia coli. Glucarpidase is a 390-amino acid homodimer protein with a molecular weight of 83 kDa. Each potency Unit corresponds to the enzymatic cleavage of 1 μmol/L of methotrexate per minute at 37°C.
Prescribed fortoxic plasma methotrexate concentrations
Chemical NameN.A.
FormulationEach vial contains 1,000 Units of glucarpidase, lactose monohydrate (10 mg), Tris-HCl (0.6 mg) and zinc acetate dihydrate (0.002 mg).
Physcial AppearanceVORAXAZE is supplied as a Sterile, preservative-free, white lyophilized powder in single-use vials
Route of AdministrationIntravenous Injection
Recommended Dosage50 Units per kg
ContraindicationN.A.
Side Effectsparaesthesias, flushing, nausea and/or vomiting, hypotension, and headache
Useful Linkhttp://www.rxlist.com/voraxaze-drug.htm http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm287997.htm http://www.drugs.com/voraxaze.html
PubMed ID24780487, 24742398, 24391395, 24132809, 23209370, 23170306
3-D StructureTh1136 (View) or (Download)