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Pharmacokinetics of Glucarpidase in Subjects With Normal and Impaired Renal Function
Author(s) -
Phillips Marc,
Smith William,
Balan Guhan,
Ward Suzanne
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007311571
Subject(s) - pharmacokinetics , medicine , volunteer , renal function , pharmacology , toxicity , impaired renal function , methotrexate , volume of distribution , urology , biology , agronomy
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 1 μ/kg) infused over 5 minutes. The mean maximum serum concentration (C max ) for glucarpidase in renally impaired subjects was 2.9 μg/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‐∞ ) was 24.5 μgxh/mL. Similar values were found in subjects with normal renal function (mean C max 3.1 μg/mL, mean t 1/2 9.0 hours, and mean AUC 0‐∞ 23.4 μgxh/mL). The results indicated little effect of renal impairment on the serum pharmacokinetics of glucarpidase.