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Population Pharmacokinetic and Pharmacodynamic Analysis of Pegloticase in Subjects With Hyperuricemia and Treatment‐Failure Gout
Author(s) -
Yue Corinne Seng,
Huang William,
Alton Michelle,
Maroli Allan N.,
Waltrip Royce W.,
Wright David,
Marco Marika
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 - 10.1177/0091270008317589
Subject(s) - hyperuricemia , gout , pharmacodynamics , medicine , pharmacokinetics , uric acid , dosing , pharmacology , population , volume of distribution , environmental health
Pegloticase is designed to convert urate into the easily excretable allantoin to treat hyperuricemia in gout. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of pegloticase in 40 gout patients. Pegloticase was administered as intravenous infusions every 2 weeks at 4‐ and 8‐mg doses or every 4 weeks at 8‐ or 12‐mg doses for 12 weeks. Serum pegloticase concentrations, plasma urate, and serum antibody response were determined. Population pharmacokinetics and pharmacodynamics analyses were performed. Data were modeled simultaneously, and covariates were investigated (age, gender, race, body weight, ideal body weight, and antibody response). The dosing regimens to maintain uric acid levels below the therapeutic target of 6 mg/dL were then predicted by the model. The pharmacokinetics were best described by a 1‐compartment linear model, while the pharmacodynamics model was fitted as a direct effect of pegloticase on uric acid concentrations with a suppressive maximum effect attributed to drug (E max ) function. Pegloticase suppressed uric acid levels up to 83%. Weight only affected clearance and volume of distribution. No covariates affected pharmacodynamics. Simulation suggests pegloticase administered at 8 mg every 2 or 4 weeks as 2‐hour intravenous infusions will maintain uric acid levels well under 6 mg/dL.