| Primary information |
|---|
| ThPP ID | Th1136 |
| Therapeutic Peptide/Protein Name | Glucarpidase |
| Sequence | ALAQKRDNVLFQAATDEQPAVIKTLEKLVNIETGTGDAEGIAAAGNFLEA view full sequnce in fasta |
| Functional Classification | Ic |
| Molecular Weight | 44016.6653 |
| Chemical Formula | C1950H3157N543O599S7 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| Half Life | Elimination half-life of 5.6 hours |
| Description | Recombinant (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/Disease | Used in patients on methotrexate treatment who have kidney dysfunction, and are experiencing an abnormally high plasma concentration of methotrexate (> 1 micromole per liter). |
| 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). |
| Toxicity | Most common adverse reactions include hypotension, flushing, nausea, vomiting, headache, and paresthesia. |
| Metabolism | Metabolism was not determined. |
| 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. |
| Clearance | In healthy patients not taking methotrexate, glucarpidase has a clearance of 7.5 mL/min. |
| Categories | Enzymes |
| Patents Number | N.A. |
| Date of Issue | N.A. |
| Date of Expiry | N.A. |
| Drug Interaction | N.A. |
| Target | Methotrexate |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Voraxaze |
| Company | BTG International |
| Brand Discription | VORAXAZE (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 for | toxic plasma methotrexate concentrations |
| Chemical Name | N.A. |
| Formulation | Each vial contains 1,000 Units of glucarpidase, lactose monohydrate (10 mg), Tris-HCl (0.6 mg) and zinc acetate dihydrate (0.002 mg). |
| Physcial Appearnce | VORAXAZE is supplied as a Sterile, preservative-free, white lyophilized powder in single-use vials |
| Route of Administration | Intravenous Injection |
| Recommended Dosage | 50 Units per kg |
| Contraindication | N.A. |
| Side Effects | paraesthesias, flushing, nausea and/or vomiting, hypotension, and headache |
| Useful Link | http://www.rxlist.com/voraxaze-drug.htm http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm287997.htm http://www.drugs.com/voraxaze.html |
| PubMed ID | 24780487, 24742398, 24391395, 24132809, 23209370, 23170306 |
| 3-D Structure | Th1136 (View) or (Download) |