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Glucarpidase
Also known as: 9074-87-7, Q5572303
Molecular Formula
Zn4+8
Molecular Weight
261.5  g/mol
InChI Key
LZQXMCNBQHANEY-UHFFFAOYSA-N

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.
1 2D Structure

Glucarpidase

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
zinc(2+)
2.1.2 InChI
InChI=1S/4Zn/q4*+2
2.1.3 InChI Key
LZQXMCNBQHANEY-UHFFFAOYSA-N
2.1.4 Canonical SMILES
[Zn+2].[Zn+2].[Zn+2].[Zn+2]
2.2 Synonyms
2.2.1 MeSH Synonyms

1. Voraxaze

2.2.2 Depositor-Supplied Synonyms

1. 9074-87-7

2. Q5572303

2.3 Create Date
2007-12-05
3 Chemical and Physical Properties
Molecular Weight 261.5 g/mol
Molecular Formula Zn4+8
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count0
Rotatable Bond Count0
Exact Mass261.70916 g/mol
Monoisotopic Mass255.71657 g/mol
Topological Polar Surface Area0 Ų
Heavy Atom Count4
Formal Charge8
Complexity0
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count4
4 Drug and Medication Information
4.1 Drug 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).


FDA Label


Treatment of methotrexate toxicity


Voraxaze is indicated to reduce toxic plasma methotrexate concentration in adults and children (aged 28 days and older) with delayed methotrexate elimination or at risk of methotrexate toxicity.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Glucarpidase acts as an antidote to toxic methotrexate levels by elminating methotrexate by a non-kidney route.


5.2 FDA Pharmacological Classification
5.2.1 Pharmacological Classes
Carboxypeptidases [CS]; Carboxypeptidase [EPC]
5.3 ATC Code

V03AF09


V - Various

V03 - All other therapeutic products

V03A - All other therapeutic products

V03AF - Detoxifying agents for antineoplastic treatment

V03AF09 - Glucarpidase


5.4 Absorption, Distribution and Excretion

Absorption

In healthy patients not taking methotrexate, the average maximum concentration for glucarpidase was 3.3 g/mL.


Route of Elimination

Route of elmination was not determined.


Volume of Distribution

Glucarpidase is likely limited to the plasma volume since its volume of distribution is 3.6 L.


Clearance

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


5.5 Metabolism/Metabolites

Metabolism was not determined.


5.6 Biological 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.


5.7 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).


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