Document Detail


Pharmacokinetics of glucarpidase in subjects with normal and impaired renal function.
MedLine Citation:
PMID:  18192538     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucarpidase (formerly known as carboxypeptidase G2 or CPG2) is being evaluated for the adjunctive treatment of patients experiencing, or at risk of, methotrexate toxicity attributable to its delayed elimination. Delayed elimination of methotrexate can occur in patients with methotrexate-induced renal toxicity. In this study, glucarpidase pharmacokinetics were assessed in volunteer subjects with normal (n = 8) and severely impaired (n = 4) renal function. Each subject received a single intravenous dose of glucarpidase 50 U/kg (equivalent to 114.5 microg/kg) infused over 5 minutes. The mean maximum serum concentration (C(max)) for glucarpidase in renally impaired subjects was 2.9 microg/mL, the mean half-life (t(1/2)) was 10.0 hours, and the mean area under the serum concentration-time curve from time zero to infinity (AUC(0-infinity)) was 24.5 microg x h/mL. Similar values were found in subjects with normal renal function (mean C(max) 3.1 microg/mL, mean t(1/2) 9.0 hours, and mean AUC(0-infinity) 23.4 microg x h/mL). The results indicated little effect of renal impairment on the serum pharmacokinetics of glucarpidase.
Authors:
Marc Phillips; William Smith; Guhan Balan; Suzanne Ward
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2008-01-11
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  48     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-20     Completed Date:  2008-05-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  279-84     Citation Subset:  IM    
Affiliation:
Protherics PLC, The Heath Business & Technical Park, Runcorn, Cheshire, UK.
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MeSH Terms
Descriptor/Qualifier:
Adult
Analysis of Variance
Area Under Curve
Enzyme-Linked Immunosorbent Assay
Female
Half-Life
Humans
Injections, Intravenous
Kidney / metabolism*
Kidney Diseases / drug therapy,  metabolism*,  physiopathology
Male
Metabolic Clearance Rate
Middle Aged
gamma-Glutamyl Hydrolase / administration & dosage,  blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
EC 3.4.19.9/gamma-Glutamyl Hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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