Half-dose glucarpidase as efficient rescue for toxic methotrexate levels in patients with acute kidney injury.
Acute kidney injury
Folinic acid
Half-dose glucarpidase
High-dose methotrexate
Methotrexate plasma concentration
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
21
07
2021
accepted:
02
10
2021
pubmed:
21
10
2021
medline:
23
2
2022
entrez:
20
10
2021
Statut:
ppublish
Résumé
High-dose methotrexate (HDMTX)-associated acute kidney injury with delayed MTX clearance has been linked to an excess in MTX-induced toxicities. Glucarpidase is a recombinant enzyme that rapidly hydrolyzes MTX into non-toxic metabolites. The recommended dose of glucarpidase is 50 U/kg, which has never been formally established in a dose finding study in humans. Few case reports, mostly in children, suggest that lower doses of glucarpidase might be equally effective in lowering MTX levels. Seven patients with toxic MTX plasma concentrations following HDMTX therapy were treated with half-dose glucarpidase (mean 25 U/kg, range 17-32 U/kg). MTX levels were measured immunologically as well as by liquid chromatography-mass spectrometry (LC-MS). Toxicities were assessed according to National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All patients experienced HDMTX-associated kidney injury (median increase in creatinine levels within 48 h after HDMTX initiation compared to baseline of 251%, range 80-455%) and showed toxic MTX plasma concentrations (range 3.1-182.4 µmol/L) before glucarpidase injection. The drug was administered 42-70 h after HDMTX initiation. Within one day after glucarpidase injection, MTX plasma concentrations decreased by ≥ 97.7% translating into levels of 0.02-2.03 µmol/L. MTX rebound was detected in plasma 42-73 h after glucarpidase initiation, but concentrations remained consistent at < 10 µmol/L. Half-dose glucarpidase seems to be effective in lowering MTX levels to concentrations manageable with continued intensified folinic acid rescue.
Identifiants
pubmed: 34669022
doi: 10.1007/s00280-021-04361-8
pii: 10.1007/s00280-021-04361-8
pmc: PMC8739299
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Recombinant Proteins
0
glucarpidase
2GFP9BJD79
gamma-Glutamyl Hydrolase
EC 3.4.19.9
Methotrexate
YL5FZ2Y5U1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
41-48Informations de copyright
© 2021. The Author(s).
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